Skip to main content
Article thumbnail
Location of Repository

An investigation of the kinase dependent functions of CRaf

By Catherine Louise Noble


The CRaf protein kinase plays a key role in relaying proliferation, differentiation and survival\ud signals from activated RAS or BRaf proteins to downstream effectors and is frequently\ud hyperactivated in human cancers. Because of this essential role in signalling, CRaf kinase\ud activity must be tightly regulated in the cell. A well-established model involves RASmediated\ud translocation of CRaf to the plasma membrane where it is activated by a series of\ud events including phosphorylation. Here, an important new mechanism of regulation that is\ud distinct from the classical model has been discovered. Through the use of kinase defective\ud crafD486A murine embryonic fibroblasts, or by the use of the Raf inhibitor sorafenib, we show\ud that the principal function of the CRaf kinase activity is autophosphorylation of serine 621.\ud This phosphorylation occurs in cis, does not involve MEK/ERK activation and is essential to\ud ensure the correct folding and stability of the protein. This novel mechanism of regulation\ud has significant implications for the control of CRaf activity in fundamental cellular processes\ud in response to signalling from the onco-proteins RAS and BRaf. Indeed here it is\ud demonstrated that CRaf promotes cell cycle progression, specifically the transition into S\ud phase. Investigation of mutant craf cells demonstrated that this form of regulation is\ud mediated in part by CRaf transcriptional repression of the CDK inhibitor p21^{CIP1}

Publisher: University of Leicester
Year: 2009
OAI identifier:

Suggested articles


  1. (2002). 14-3-3 antagonizes Ras-mediated Raf-1 recruitment to the plasma membrane to maintain signaling fidelity.
  2. (1998). 14-3-3 facilitates Ras-dependent Raf-1 activation in vitro and in vivo.
  3. (1995). 14-3-3 is not essential for Raf-1 function: identification of Raf-1 proteins that are biologically activated in a 14-3-3- and Ras-independent manner.
  4. (1998). 14-3-3 proteins are required for maintenance of Raf-1 phosphorylation and kinase activity.
  5. (1995). 14-3-3 proteins associate with cdc25 phosphatases.
  6. (2001). 14-3-3 proteins; bringing new definitions to scaffolding.
  7. (2000). 14-3-3 proteins: structure, function, and regulation.
  8. (1997). 14-3-3 zeta negatively regulates raf-1 activity by interactions with the Raf-1 cysteine-rich domain.
  9. (1992). 95-kilodalton B-Raf serine/threonine kinase: identification of the protein and its major autophosphorylation site.
  10. (1991). A CAAX or a CAAL motif and a second signal are sufficient for plasma membrane targeting of ras proteins.
  11. (2006). A chaperone-dependent GSK3b transitional intermediate mediates activation-loop autophosphorylation.
  12. (1998). A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation.
  13. (1995). A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells.
  14. (1998). A dimeric 14-3-3 protein is an essential cofactor for Raf kinase activity.
  15. (1993). A dominant-negative mutant of raf blocks mitogen-activated protein kinase activation by growth factors and oncogenic p21ras.
  16. (1993). A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity.
  17. (1998). A measure of the mitotic index: studies of the abundance and half-life of p34cdc2 in cultured cells and normal and neoplastic tissues.
  18. (1994). A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase.
  19. (2007). A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors.
  20. (1993). A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
  21. (2001). A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment.
  22. (1988). A novel oncogene related to c-mil is transduced in chicken neuroretina cells induced to proliferate by infection with an avian lymphomatosis virus.
  23. (2006). A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity.
  24. (1991). A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression.
  25. (1990). A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane.
  26. (1995). A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function.
  27. (2006). A Ras-induced conformational switch in the Ras activator Son of sevenless.
  28. (2000). A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor beta -induced cell-cycle arrest.
  29. (2005). A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression.
  30. (1997). A-Raf kinase is a new interacting partner of protein kinase CK2 beta subunit.
  31. (1994). Absence of activating mutations of the RAF1 protooncogene in human lung cancer.
  32. (2005). Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin.
  33. (2005). Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin. Cancer Res.
  34. (1996). Activated Ras displaces 14-3-3 protein from the amino terminus of c-Raf-1.
  35. (1992). Activating transcription factor-2 DNAbinding activity is stimulated by phosphorylation catalyzed by p42 and p54 microtubule-associated protein kinases.
  36. (1998). Activation and repression of p21(WAF1/CIP1) transcription by RB binding proteins.
  37. (2000). Activation of B-Raf kinase requires phosphorylation of the conserved residues
  38. (1996). Activation of brain B-Raf protein kinase by Rap1B small GTP-binding protein.
  39. (1992). Activation of extracellular signal-regulated kinase, ERK2, by p21ras oncoprotein.
  40. (1987). Activation of human raf transforming genes by deletion of normal amino-terminal coding sequences.
  41. (1992). Activation of mitogen-activated protein kinase kinase by vRaf in NIH 3T3 cells and in vitro.
  42. (1994). Activation of Raf as a result of recruitment to the plasma membrane.
  43. (1994). Activation of Raf-1 by 14-3-3 proteins.
  44. (2004). Activation of RB/E2F signaling pathway is required for the modulation of hepatitis C virus core protein-induced cell growth in liver and non-liver cells.
  45. (1992). Activation of the MAP kinase pathway by the protein kinase raf.
  46. (1996). Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization.
  47. (1996). Activation of the Raf-1/MAP kinase cascade is not sufficient for Ras transformation of RIE-1 epithelial cells.
  48. (1999). Activation of the Raf/MAP kinase cascade by the Ras-related protein TC21 is required for the TC21-mediated transformation of NIH 3T3 cells.
  49. (2005). Activationloop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs.
  50. (2001). Active Ras induces heterodimerization of cRaf and BRaf.
  51. (2003). Affinity with Raf is sufficient for Ras to efficiently induce rat mammary carcinomas.
  52. (2005). An acylation cycle regulates localization and activity of palmitoylated Ras isoforms.
  53. (1999). An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9.
  54. (1997). An intact Raf zinc finger is required for optimal binding to processed Ras and for ras-dependent Raf activation in situ.
  55. (1986). Analysis of homologous recombination in cultured mammalian cells in transient expression and stable transformation assays.
  56. (1999). Analysis of mammalian cisregulatory DNA elements by homologous recombination.
  57. (2001). Analysis of the transcriptional program induced by Raf in epithelial cells.
  58. (1997). Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: a p53-independent induction of p21WAF1/CIP1 via C/EBPbeta.
  59. (1997). AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression.
  60. (1994). Apoptosis regulation by interaction of
  61. (1997). Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAF1/CiP1.
  62. (1997). as AMPactivated protein kinase.
  63. (1998). Autoregulation of the Raf-1 serine/threonine kinase.
  64. (2004). B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibers in fibroblasts.
  65. (2005). B-Raf and Raf-1 are regulated by distinct autoregulatory mechanisms.
  66. (1999). B-Raf inhibits programmed cell death downstream of cytochrome c release from mitochondria by activating the MEK/Erk pathway.
  67. (2004). B-Raf is dispensable for KRas-mediated oncogenesis in human cancer cells.
  68. (1988). B-raf, a new member of the raf family, is activated by DNA rearrangement.
  69. (2006). Back to the roots: the remarkable RAF oncogene story.
  70. (2001). Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth.
  71. (1997). Bcl-2 does not require Raf kinase activity for its death-protective function.
  72. (1999). BCL-2 family members and the mitochondria in apoptosis.
  73. (1996). Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1.
  74. (1994). Binding of 14-3-3 proteins to the protein kinase Raf and effects on its activation.
  75. (1995). Biochemical analysis of MEK activation in NIH3T3 fibroblasts. Identification of B-Raf and other activators.
  76. (2003). BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets.
  77. (2003). BRAF and K-ras gene mutations in human pancreatic cancers.
  78. (2002). BRAF and RAS mutations in human lung cancer and melanoma.
  79. (2003). BRAF mutations in metastatic melanoma: a possible association with clinical outcome.
  80. (2003). BRAF mutations in papillary carcinomas of the thyroid.
  81. (1997). Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line.
  82. (2001). C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1.
  83. (1997). cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway.
  84. (2004). Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis.
  85. (1996). CCAAT/enhancer-binding protein alpha (C/EBP alpha) inhibits cell proliferation through the p21 (WAF-1/CIP-1/SDI-1) protein.
  86. (2004). Cdc25 phosphatases and cancer.
  87. (1994). Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme.
  88. (2002). Cell adhesion protects c-Raf-1 against ubiquitin-dependent degradation by the proteasome.
  89. (1997). Cell anchorage permits efficient signal transduction between ras and its downstream kinases.
  90. (2003). Cell cycle and apoptosis.
  91. (1997). Cell cycle arrest mediated by the MEK/mitogenactivated protein kinase pathway.
  92. (2000). Cell cycle regulation by the Cdc25 phosphatase family.
  93. (1996). Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1.
  94. (1999). Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms.
  95. (1995). Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1.
  96. (1994). Characterization of a 78-residue fragment of c-Raf-1 that comprises a minimal binding domain for the interaction with Ras-GTP.
  97. (1996). Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro.
  98. (1986). Characterization of murine A-raf, a new oncogene related to the v-raf oncogene.
  99. (1999). Characterization of Raf-1 activation in mitosis.
  100. (1994). Chemical shift assignments and folding topology of the Ras-binding domain of human Raf-1 as determined by heteronuclear three-dimensional NMR spectroscopy.
  101. (2003). CHIP: a link between the chaperone and proteasome systems.
  102. (2003). CHIP: a quality-control E3 ligase collaborating with molecular chaperones.
  103. (2007). CK2 Is a component of the KSR1 scaffold complex that contributes to Raf kinase activation.
  104. (1999). CK2, a protein kinase of the next millennium.
  105. (2005). CNK1 is a scaffold protein that regulates Src-mediated Raf-1 activation.
  106. (1998). Cofactor-induced modulation of the functional specificity of the molecular chaperone Hsc70. Biol Chem,
  107. (1994). Compartmentalization of SHC, GRB2 and mSOS, and hyperphosphorylation of Raf-1 by EGF but not insulin in liver parenchyma.
  108. (1995). Compartmentalized signal transduction by receptor tyrosine kinases.
  109. (1990). Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies.
  110. (1993). Complex formation between RAS and RAF and other protein kinases.
  111. (1997). Conditional expression of the mitogen-activated protein kinase (MAPK) phosphatase MKP-1 preferentially inhibits p38 MAPK and stress-activated protein kinase in U937 cells.
  112. (1993). Conditional transformation of cells and rapid activation of the mitogen-activated protein kinase cascade by an estradiol-dependent human raf-1 protein kinase.
  113. (1995). Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display different biological and biochemical properties in NIH 3T3 cells.
  114. (1999). Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors.
  115. (2004). Constitutive activation of the Ras-Raf signaling pathway in metastatic melanoma is associated with poor prognosis.
  116. (2004). Constitutive expression of E2F-1 leads to p21-dependent cell cycle arrest in S phase of the cell cycle.
  117. (1991). Control of c-myc regulation in normal and neoplastic cells.
  118. (1990). Control of mammalian cell proliferation.
  119. (1996). Control of the ERK MAP kinase cascade by Ras and Raf.
  120. (1997). Cooperating oncogenes converge to regulate cyclin/cdk complexes.
  121. (2001). Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling.
  122. (1996). Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase.
  123. (1993). cPLA2 is phosphorylated and activated by MAP kinase.
  124. (2008). CRAF autophosphorylation of serine 621 is required to prevent its proteasome-mediated degradation.
  125. (1998). Craf-1 protein kinase is essential for mouse development.
  126. (1994). Critical binding and regulatory interactions between Ras and Raf occur through a small, stable N-terminal domain of Raf and specific Ras effector residues.
  127. (1993). Critical tyrosine residues regulate the enzymatic and biological activity of Raf-1 kinase.
  128. (1994). CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factorinduced activation of Ras in PC12 cells.
  129. (1995). Crystal structure of the zeta isoform of the 14-3-3 protein.
  130. (1999). Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells.
  131. (2002). Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms.
  132. (1991). Cyclic AMP second messenger systems.
  133. (2002). Cyclic AMP-dependent kinase regulates Raf-1 kinase mainly by phosphorylation of serine 259.
  134. (2001). Cyclin D1 expression in dysplastic nevi: an immunohistochemical study.
  135. (1996). Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway.
  136. (2003). Cyclin E ablation in the mouse.
  137. (2001). Cyclin-dependent kinase 2 nucleocytoplasmic translocation is regulated by extracellular regulated kinase.
  138. (1995). Cysteine-rich region of Raf-1 interacts with activator domain of post-translationally modified Ha-Ras.
  139. (1996). Cytoplasmic localization of mitogen-activated protein kinase kinase directed by its NH2-terminal, leucine-rich short amino acid sequence, which acts as a nuclear export signal.
  140. (2001). Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER2/neu-overexpressing cells.
  141. (2006). Cytoplasmic p21WAF1/CIP1 correlates with Akt activation and poor response to tamoxifen in breast cancer.
  142. (1994). D-type cyclin-dependent kinase activity in mammalian cells.
  143. (1989). Definition of the human raf amino-terminal regulatory region by deletion mutagenesis.
  144. (2005). Depalmitoylated Ras traffics to and from the Golgi complex via a nonvesicular pathway.
  145. (1996). Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEKmitogen-activated protein kinase signalling pathway.
  146. (2002). Development of mice expressing a single D-type cyclin.
  147. (1996). Difference in the mechanism of interaction of Raf-1 and B-Raf with H-Ras.
  148. (1995). Differential c-myc, c-jun, c-raf and p53 expression in squamous cell carcinoma of the head and neck: implication in drug and radioresistance.
  149. (1994). Differential Raf requirement for activation of mitogen-activated protein kinase by growth factors, phorbol esters, and calcium.
  150. (2007). Differential regulation of B-raf isoforms by phosphorylation and autoinhibitory mechanisms.
  151. (1997). Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic ras and tyrosine kinases.
  152. (1996). Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase.
  153. (1993). Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4.
  154. (1993). Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro.
  155. (1995). Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association.
  156. (2004). Disruption of the Rb--Raf-1 interaction inhibits tumor growth and angiogenesis.
  157. (2000). Distinct isoforms of the cofactor BAG-1 differentially affect Hsc70 chaperone function.
  158. (1998). Distinct mechanisms mediate the initial and sustained phases of integrin-mediated activation of the Raf/MEK/mitogen-activated protein kinase cascade.
  159. (2002). Distinct requirements for Ras oncogenesis in human versus mouse cells.
  160. (1993). Distinct roles for cyclin-dependent kinases in cell cycle control.
  161. (2004). Dynamic changes in C-Raf phosphorylation and 14-3-3 protein binding in response to growth factor stimulation: differential roles of 14-3-3 protein binding sites.
  162. (1998). Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication.
  163. (1999). Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta.
  164. (2001). Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene.
  165. (2004). Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects.
  166. (1997). Endothelial apoptosis in Braf-deficient mice.
  167. (1994). Enzymatic characteristics of the c-Raf-1 protein kinase.
  168. (1991). Epidermal growth factor (EGF) receptor T669 peptide kinase from 3T3-L1 cells is an EGF-stimulated "MAP" kinase.
  169. (2000). Epidermal growth factor receptor activation of calpain is required for fibroblast motility and occurs via an ERK/MAP kinase signaling pathway.
  170. (2006). Erbin inhibits RAF activation by disrupting the sur8-Ras-Raf complex.
  171. (2003). Erbin suppresses the MAP kinase pathway.
  172. (2002). ERK signalling and oncogene transformation are not impaired in cells lacking A-Raf.
  173. (2006). ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially.
  174. (2007). ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL.
  175. (2002). ERK2 enters the nucleus by a carrier-independent mechanism.
  176. (2001). Erythropoietin-stimulated Raf-1 tyrosine phosphorylation is associated with the tyrosine kinase Lyn in J2E erythroleukemic cells.
  177. (2003). Essential role for ERK2 mitogenactivated protein kinase in placental development.
  178. (2006). Essential role of B-Raf in ERK activation during extraembryonic development.
  179. (2008). Essential role of BRaf in oligodendrocyte maturation and myelination during postnatal central nervous system development.
  180. (2003). Essential role of Raf in Ras transformation and deregulation of matrix metalloproteinase expression in ovarian epithelial cells.
  181. (1981). Establishment in culture of pluripotential cells from mouse embryos.
  182. (2001). Evidence for existence of a nuclear pore complex-mediated, cytosol-independent pathway of nuclear translocation of ERK MAP kinase in permeabilized cells.
  183. (1998). Exposure of human vascular smooth muscle cells to Raf-1 antisense oligodeoxynucleotides: cellular responses and pharmacodynamic implications.
  184. (2000). Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion.
  185. (1995). Expression and activation of B-Raf kinase isoforms in human and murine leukemia cell lines.
  186. (1998). Expression and location of Hsp70/Hscbinding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines.
  187. (2005). Expression of endogenous oncogenic V600EB-raf induces proliferation and developmental defects in mice and transformation of primary fibroblasts.
  188. (1990). Expression of raf family protooncogenes in normal mouse tissues.
  189. (2000). Expression of the A-raf proto-oncogene in the normal adult and embryonic mouse.
  190. (1984). Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines.
  191. (1998). Fos family members induce cell cycle entry by activating cyclin D1.
  192. (1999). Four human ras homologs differ in their abilities to activate Raf-1, induce transformation, and stimulate cell motility.
  193. (2003). Functional analysis of mutations within the kinase activation segment of B-Raf in human colorectal tumors.
  194. (1995). Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter.
  195. (1995). Functional mapping of the N-terminal regulatory domain in the human Raf-1 protein kinase.
  196. (1997). Geldanamycin-induced destabilization of Raf-1 involves the proteasome.
  197. (1986). Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector.
  198. (1999). Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinasedependent pathway in brain slices.
  199. (1993). Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase (p45mapkk) in fibroblasts.
  200. (1999). Growth inhibition by CDK-cyclin and PCNA binding domains of p21 occurs by distinct mechanisms and is regulated by ubiquitin-proteasome pathway.
  201. (1997). GrpE-like regulation of the hsc70 chaperone by the anti-apoptotic protein BAG-1.
  202. (1993). GTP-dependent association of Raf-1 with Ha-Ras: identification of Raf as a target downstream of Ras in mammalian cells.
  203. (1995). Guanine nucleotide exchange factors: activators of the Ras superfamily of proteins.
  204. (2004). Guilty as charged: B-RAF is a human oncogene.
  205. (1993). H-ras and raf-1 cooperate in transformation of NIH3T3 fibroblasts.
  206. (2003). High frequency of BRAF mutations in nevi.
  207. (2003). High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.
  208. (1997). High-intensity Raf signal causes cell cycle arrest mediated by p21Cip1.
  209. (1998). High-intensity Raf signals convert mitotic cell cycling into cellular growth.
  210. (1997). Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites.
  211. (1998). Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins.
  212. (1995). Human cyclin E, a nuclear protein essential for the G1 to S phase transition.
  213. (1995). Human cyclin E, a nuclear protein essential for the G1-to-S phase transition.
  214. (2001). Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line.
  215. (2001). Identification of a C-terminal region that regulates mitogen-activated protein kinase kinase-1 cytoplasmic localization and ERK activation.
  216. (1994). Identification of a latent MAP kinase kinase kinase in PC12 cells as B-raf.
  217. (1995). Identification of binding domains on the p21Cip1 cyclin-dependent kinase inhibitor.
  218. (1999). Identification of CHIP, a novel tetratricopeptide repeatcontaining protein that interacts with heat shock proteins and negatively regulates chaperone functions.
  219. (1994). Identification of discrete segments of human Raf-1 kinase critical for high affinity binding to Ha-Ras.
  220. (2006). Identification of novel in vivo Raf-1 phosphorylation sites mediating positive feedback Raf-1 regulation by extracellular signal-regulated kinase.
  221. (2005). Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities and for MEK binding.
  222. (1996). Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system.
  223. (1995). Identification of the 14.3.3 zeta domains important for self-association and Raf binding.
  224. (1993). Identification of the major phosphorylation sites of the Raf-1 kinase.
  225. (2004). In ovarian neoplasms, BRAF, but not KRAS, mutations are restricted to low-grade serous tumours.
  226. (2001). Inc., SC-408), CRaf (BD Biosciences, 610152), BRaf (Santa Cruz Biotechnology, Inc., SC-5284), actin (Sigma, A2103), GAPDH (Millipore, MAB374), MEK1/2 (Cell Signaling Technology, 9122), ERK2 (Santa Cruz Biotechnology, Inc.,
  227. (1997). Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways.
  228. (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c.
  229. (2001). Induction of beta3-integrin gene expression by sustained activation of the Ras-regulated Raf-MEKextracellular signal-regulated kinase signaling pathway.
  230. (1997). Induction of cell proliferation in quiescent NIH 3T3 cells by oncogenic c-Raf-1.
  231. (1997). Induction of p27Kip1 degradation and anchorage independence by Ras through the MAP kinase signaling pathway.
  232. (2003). Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.
  233. (1999). Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after gamma-irradiation.
  234. (1995). Inhibition of cyclin-dependent kinases by p21.
  235. (1988). Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides.
  236. (1998). Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21(WAF1/CIP1) in human prostate carcinoma cells.
  237. (1993). Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3',5'-monophosphate.
  238. (1997). Inhibition of the Raf-1 kinase by cyclic AMP agonists causes apoptosis of v-abltransformed cells.
  239. (1995). Inhibitors of mammalian G1 cyclin-dependent kinases.
  240. (1985). Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination.
  241. (1990). Insulin activates the kinase activity of the Raf-1 proto-oncogene by increasing its serine phosphorylation.
  242. (1988). Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II.
  243. (1998). Integrin alphavbeta3 requirement for sustained mitogen-activated protein kinase activity during angiogenesis.
  244. (1996). Integrin-mediated activation of MEK and mitogen-activated protein kinase is independent of Ras [corrected].
  245. (2002). Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1.
  246. (1998). Interaction between the protein kinase B-Raf and the alpha-subunit of the 11S proteasome regulator.
  247. (1996). Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine.
  248. (1984). Interaction of the bacteriophage P1 recombinase Cre with the recombining site loxP.
  249. (1994). Interaction of the protein kinase Raf-1 with 14-3-3 proteins.
  250. (1999). Interactions of c-Raf-1 with phosphatidylserine and 14-3-3.
  251. (1996). Involvement of p21cip-1 and p27kip-1 in the molecular mechanisms of steel factorinduced proliferative synergy in vitro and of p21cip-1 in the maintenance of stem/progenitor cells in vivo.
  252. (1992). Involvement of p21ras in activation of extracellular signal-regulated kinase 2.
  253. (1997). Involvement of the Sp3 transcription factor in induction of p21Cip1/WAF1 in keratinocyte differentiation.
  254. (2000). Isoformspecific localization of A-RAF in mitochondria.
  255. (1991). Isolation and characterization of two growth factor-stimulated protein kinases that phosphorylate the epidermal growth factor receptor at threonine 669.
  256. (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.
  257. (1999). Isotype-specific functions of Raf kinases.
  258. (2002). Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo.
  259. (1999). Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization.
  260. (1997). Kinase suppressor of Ras is ceramide-activated protein kinase.
  261. (2001). Kinase suppressor of Ras signals through Thr269 of c-Raf-1.
  262. (1998). Kinetic analyses of mutations in the glycine-rich loop of cAMP-dependent protein kinase.
  263. (2002). Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory.
  264. (2002). KSR is a scaffold required for activation of the ERK/MAPK module.
  265. (2001). KSR: a MAPK scaffold of the Ras pathway?
  266. (1995). Lack of evidence for the activation of the Ras/Raf mitogenic pathway by 14-3-3 proteins in mammalian cells.
  267. (2002). LATS1 tumor suppressor regulates G2/M transition and apoptosis.
  268. (2003). Lats2, a putative tumor suppressor, inhibits G1/S transition.
  269. (2002). Localization of the MP1-MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction.
  270. (1996). Loss of the p16INK4a and p15INK4b genes, as well as neighboring 9p21 markers, in sporadic melanoma.
  271. (2000). Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein.
  272. (1992). Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis.
  273. (1993). Mammalian Ras interacts directly with the serine/threonine kinase Raf.
  274. (2003). Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1. Cell Cycle,
  275. (2005). Mammalian Sterile 20-like kinases in tumor suppression: an emerging pathway.
  276. (2003). MDM2 promotes p21waf1/cip1 proteasomal turnover independently of ubiquitylation.
  277. (2000). Meaningful relationships: the regulation of the Ras/Raf/MEK/ ERK pathway by protein interactions.
  278. (2000). Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions.
  279. (2004). Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.
  280. (2004). Mechanism of activation of the RAF-ERK signaling pathway by oncogenicmutations of B-RAF.
  281. (1994). Mechanism of inhibition of Raf-1 by protein kinase A.
  282. (2000). Mechanism of suppression of the Raf/MEK/extracellular signalregulated kinase pathway by the raf kinase inhibitor protein.
  283. (2004). Mechanisms of human papillomavirusinduced oncogenesis.
  284. (2001). Mechanisms underlying ubiquitination.
  285. (2001). MEK kinase activity is not necessary for Raf-1 function.
  286. (2003). Mek2 is dispensable for mouse growth and development.
  287. (1999). Melanoma cell autonomous growth: the Rb/E2F pathway.
  288. (2006). Methylglyoxal downregulates Raf-1 protein through a ubiquitination-mediated mechanism.
  289. (1992). Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state.
  290. (1994). Mitogen-activated protein kinase/extracellular signal-regulated protein kinase activation by oncogenes, serum, and 12-Otetradecanoylphorbol-13-acetate requires Raf and is necessary for transformation.
  291. (1997). Mitogenactivated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2.
  292. (1995). Mitogenesis by v-Src: fluctuations throughout G1 of classical immediate early AP-1 and mitogen-activated protein kinase responses that parallel the need for the oncoprotein.
  293. (2000). Mitogenic signaling of Ras is regulated by differential interaction with Raf isozymes.
  294. (1998). Mitotic Raf-1 is stimulated independently of Ras and is active in the cytoplasm.
  295. (1998). Modulation of kinase activity and oncogenic properties by alternative splicing reveals a novel regulatory mechanism for B-Raf.
  296. (2005). Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein.
  297. (1997). Molecular cloning and functional characterization of a novel mitogen-activated protein kinase phosphatase,
  298. (1999). Multiple abnormalities of the p16INK4a-pRb regulatory pathway in cultured melanoma cells.
  299. (1999). Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase.
  300. (1990). Mutational activation of c-raf-1 and definition of the minimal transforming sequence.
  301. (2005). Mutational analysis of the ARAF gene in human cancers.
  302. (2003). Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma.
  303. (2005). Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with BRAF.
  304. (2003). Mutations of the BRAF gene in benign and malignant melanocytic lesions.
  305. (2002). Mutations of the BRAF gene in human cancer.
  306. (2001). Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3.
  307. (1996). Negative regulation of Raf-1 by phosphorylation of serine 621.
  308. (2000). Negative regulation of the serine/threonine kinase B-Raf by Akt.
  309. (1995). Nerve growth factor-induced growth arrest and induction of p21Cip1/WAF1 in NIH-3T3 cells expressing TrkA.
  310. (1996). Nerve growth factor-mediated activation of the mitogen-activated protein (MAP) kinase cascade involves a signaling complex containing B-Raf and HSP90.
  311. (1997). New functional activities for the p21 family of CDK inhibitors.
  312. (1996). Newly identified stress-responsive protein kinases,
  313. (1993). Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of cRaf-1.
  314. (2005). Novel C-Raf phosphorylation sites: serine 296 and 301 participate in Raf regulation.
  315. (1999). Novel membrane-targeted ERK1 and ERK2 chimeras which act as dominant negative, isotype-specific mitogen-activated protein kinase inhibitors of Ras-Raf-mediated transcriptional activation of c-fos in NIH 3T3 cells.
  316. (1992). Nuclear localization and regulation of erk- and rsk-encoded protein kinases.
  317. (1997). Nuclear translocation of mitogen-activated protein kinase kinase (MEK1) in response to mitogenic stimulation.
  318. (1996). Oligomerization activates c-Raf-1 through a Ras-dependent mechanism.
  319. (1998). Oncogenes, growth factors and phorbol esters regulate Raf-1 through common mechanisms.
  320. (2001). Oncogenic Ras blocks anoikis by activation of a novel effector pathway independent of phosphatidylinositol 3-kinase.
  321. (1997). Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.
  322. (2000). Opposing effects of Ras on p53: transcriptional activation of mdm2 and induction of p19ARF.
  323. (2003). Opposite long-term regulation of c-Myc and p27Kip1 through overactivation of Raf-1 and the MEK/ERK module in proliferating human choroidal melanoma cells.
  324. (2004). Over-expression of c-raf-1 proto-oncogene in liver cirrhosis and hepatocellular carcinoma.
  325. (1994). Overexpression of the Raf-1 proto-oncogene in human myeloid leukemia.
  326. (2000). Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis.
  327. (1982). P1 site-specific recombination: nucleotide sequence of the recombining sites.
  328. (2006). p14-MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis.
  329. (1998). p16INK4a expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma.
  330. (1995). p21 is necessary for the p53-mediated G1 arrest in human cancer cells.
  331. (1994). p21-containing cyclin kinases exist in both active and inactive states.
  332. (1999). p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function.
  333. (1998). p50(cdc37) binds directly to the catalytic domain of Raf as well as to a site on hsp90 that is topologically adjacent to the tetratricopeptide repeat binding site.
  334. (1995). p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage.
  335. (2003). p53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1.
  336. (1999). p90(RSK) blocks badmediated cell death via a protein kinase C-dependent pathway.
  337. (1994). Partial purification of a mitogen-activated protein kinase kinase activator from bovine brain. Identification as B-Raf or a B-Raf-associated activity.
  338. (2001). PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase.
  339. (1996). PEST sequences and regulation by proteolysis.
  340. (1996). Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc Natl Acad Sci
  341. (2000). Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338.
  342. (1994). Phosphatidylinositol3-OH kinase as a direct target of Ras.
  343. (1993). Phosphorylation and activation of a high molecular weight form of phospholipase A2 by p42 microtubule-associated protein 2 kinase and protein kinase C.
  344. (1999). Phosphorylation and regulation of Raf by Akt (protein kinase
  345. (1991). Phosphorylation of c-jun mediated by MAP kinases.
  346. (2003). Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization.
  347. (2000). Phosphorylation of serine 43 is not required for inhibition of c-Raf kinase by the cAMP-dependent protein kinase.
  348. (1993). Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase.
  349. (1992). Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter.
  350. (1993). Phosphorylation of Xenopus mitogenactivated protein (MAP) kinase kinase by MAP kinase kinase kinase and MAP kinase.
  351. (2001). Phosphorylation site specificity of the Pak-mediated regulation of Raf-1 and cooperativity with Src.
  352. (2001). Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase.
  353. (2004). Phosphorylation/cytoplasmic localization of p21Cip1/WAF1 is associated with HER2/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients.
  354. (1997). Physical association with ras enhances activation of membrane-bound raf (RafCAAX).
  355. (2006). PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis.
  356. (2001). Positive and negative regulation of Raf kinase activity and function by phosphorylation.
  357. (1996). Post-natal lethality and neurological and gastrointestinal defects in mice with targeted disruption of the A-Raf protein kinase gene.
  358. (1991). Pro-Leu-Ser/Thr-Pro is a consensus primary sequence for substrate protein phosphorylation. Characterization of the phosphorylation of c-myc and c-jun proteins by an epidermal growth factor receptor threonine 669 protein kinase.
  359. (2003). Proliferation of cancer cells despite CDK2 inhibition.
  360. (1998). Prolonged vs transient roles for early cell cycle signaling components.
  361. (2000). Proteasomal turnover of p21Cip1 does not require p21Cip1 ubiquitination.
  362. (2003). Proteasome-mediated degradation of p21 via N-terminal ubiquitinylation.
  363. (1996). Proteasomedependent regulation of p21WAF1/CIP1 expression.
  364. (2003). Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras.
  365. (1993). Protein kinase C alpha activates RAF-1 by direct phosphorylation.
  366. (1997). Protein kinase CK2.
  367. (1995). Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.
  368. (2003). Protein phosphatase 2A positively regulates Ras signaling by dephosphorylating KSR1 and Raf-1 on critical 14-3-3 binding sites.
  369. (2001). Protein phosphatases 1 and 2A promote Raf-1 activation by regulating 14-3-3 interactions.
  370. (2005). Protein-protein interactions in the regulation of the extracellular signal-regulated kinase.
  371. (1995). Purification of a Ras-dependent mitogen-activated protein kinase kinase kinase from bovine brain cytosol and its identification as a complex of B-Raf and 14-3-3 proteins.
  372. (1994). Purification of the AMP-activated protein kinase on ATP-gammasepharose and analysis of its subunit structure.
  373. (1995). Quantitative analysis of the complex between p21ras and the Ras-binding domain of the human Raf-1 protein kinase.
  374. (2003). RAF antisense oligonucleotide as a tumor radiosensitizer.
  375. (2003). Raf kinases in lung tumor development.
  376. (1994). Raf meets Ras: completing the framework of a signal transduction pathway.
  377. (1990). raf oncogenes in carcinogenesis.
  378. (1995). Raf phosphorylates p53 in vitro and potentiates p53-dependent transcriptional transactivation in vivo.
  379. (2003). Raf proteins and cancer: B-Raf is identified as a mutational target.
  380. (2005). Raf-1 expression may influence progression to androgen insensitive prostate cancer.
  381. (1991). Raf-1 is a potential substrate for mitogen-activated protein kinase in vivo.
  382. (1995). Raf-1 is activated during mitosis.
  383. (2004). Raf-1 is not required for megakaryocytopoiesis or TPO-induced ERK phosphorylation.
  384. (1996). Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Raf-1 in 12-Otetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells.
  385. (1998). Raf-1 physically interacts with Rb and regulates its function: a link between mitogenic signaling and cell cycle regulation.
  386. (2001). Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism.
  387. (2001). Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEKERK independent mechanism.
  388. (1991). Raf-1 protein kinase is required for growth of induced NIH/3T3 cells.
  389. (2005). Raf-1 regulates Rho signaling and cell migration.
  390. (2005). Raf-1 sets the threshold of Fas sensitivity by modulating Rok-alpha signaling.
  391. (2000). Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation.
  392. (1997). Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1.
  393. (1995). Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation.
  394. (2005). Raf1 sets the threshold of Fas sensitivity by modulating Rok-alpha signaling.
  395. (1995). Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes.
  396. (1997). Rapid phosphorylation of Ets-2 accompanies mitogenactivated protein kinase activation and the induction of heparin-binding epidermal growth factor gene expression by oncogenic Raf-1.
  397. (1994). RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2.
  398. (2005). Ras binding opens c-Raf to expose the docking site for mitogen-activated protein kinase kinase.
  399. (1992). Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases.
  400. (1992). ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK.
  401. (1989). ras oncogenes in human cancer: a review.
  402. (2003). Ras proteins: different signals from different locations.
  403. (1995). Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation.
  404. (2004). Ras regulates assembly of mitogenic signalling complexes through the effector protein IMP.
  405. (2002). Ras signalling on the endoplasmic reticulum and the Golgi.
  406. (2003). Ras-effector interactions: after one decade.
  407. (1999). Receptor signaling: when dimerization is not enough.
  408. (2006). Regulation and role of Raf-1/B-Raf heterodimerization.
  409. (1996). Regulation of 5'-AMP-activated protein kinase activity by the noncatalytic beta and gamma subunits.
  410. (1998). Regulation of c-myc expression by Ras/Raf signalling.
  411. (1997). Regulation of cell motility by mitogen-activated protein kinase.
  412. (1996). Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.
  413. (2001). Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking.
  414. (1991). Regulation of p21ras activity.
  415. (2001). Regulation of p53 expression by the RAS-MAP kinase pathway.
  416. (2005). Regulation of Raf-1 by direct feedback phosphorylation.
  417. (2006). Regulation of ras signaling dynamics by Sosmediated positive feedback.
  418. (1994). Regulation of signal transduction and signal diversity by receptor oligomerization.
  419. (1998). Regulation of the cdk inhibitor p21 gene during cell cycle progression is under the control of the transcription factor E2F.
  420. (1993). Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts.
  421. (1995). Regulation of the cyclin E gene by transcription factor E2F1.
  422. (1997). Regulation of the cyclindependent kinase inhibitor p27 by degradation and phosphorylation.
  423. (2004). Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.
  424. (2000). Regulation of the protein kinase Raf-1 by oncogenic Ras through phosphatidylinositol 3-kinase, Cdc42/Rac and Pak.
  425. (2000). Regulation of the Raf-1 kinase domain by phosphorylation and 14-3-3 association.
  426. (2004). Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis?
  427. (1997). Requirement for Drosophila 14-3-3 zeta in Raf-dependent photoreceptor development.
  428. (1994). Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane.
  429. (1996). Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle.
  430. (1998). Requirement of Ras-GTP-Raf complexes for activation of Raf-1 by protein kinase
  431. (1992). Retinoblastoma-repression of E2F-dependent transcription depends on the ability of the retinoblastoma protein to interact with E2F and is abrogated by the adenovirus ElA oncoprotein.
  432. (1995). Reversal of Raf-1 activation by purified and membrane-associated protein phosphatases.
  433. (2005). Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin.
  434. (2003). Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma.
  435. (2001). Role of MAP kinase pathways in primitive neuroectodermal tumors.
  436. (1994). Role of Shc in the activation of Ras in response to epidermal growth factor and nerve growth factor.
  437. (1997). Role of the glycine triad in the ATP-binding site of cAMP-dependent protein kinase.
  438. (2004). Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1.
  439. (2003). Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase.
  440. (1995). Role of the ubiquitinproteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27.
  441. (1995). S-phase phosphorylation of lamin B2. Fed Eur Biochem Soc Lett,
  442. (2005). Second nature: biological functions of the Raf-1 "kinase".
  443. (2004). Sef is a spatial regulator for Ras/MAP kinase signaling.
  444. (1996). Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela cells.
  445. (1998). Selective deletion of exon 1 beta of the p19ARF gene in metastatic melanoma cell lines.
  446. (1996). Selective interaction of JNK protein kinase isoforms with transcription factors.
  447. (1995). Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA.
  448. (2003). Serine 338 phosphorylation is dispensable for activation of c-Raf1.
  449. (1999). Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf activation.
  450. (1996). Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L).
  451. (1992). Signal transduction within the nucleus by mitogen-activated protein kinase.
  452. (1974). Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA.
  453. (1995). Similar substrate recognition motifs for mammalian AMP-activated protein kinase, higher plant HMGCoA reductase kinase-A, yeast SNF1, and mammalian calmodulin-dependent protein kinase I.
  454. (2002). Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia.
  455. (2005). Small interfering RNA targeting Raf-1 inhibits tumor growth in vitro and in vivo.
  456. (2002). Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR).
  457. (2001). Specific function of B-Raf in mediating survival of embryonic motoneurons and sensory neurons.
  458. (1995). Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.
  459. (2001). Spred is a Sprouty-related suppressor of Ras signalling.
  460. (2002). Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway.
  461. (2002). Stimulation of
  462. (1994). Stimulatory effects of yeast and mammalian 14-3-3 proteins on the Raf protein kinase.
  463. (2004). Structural analysis of autoinhibition in the Ras activator Son of sevenless.
  464. (2003). Structural basis for the autoinhibition of c-Abl tyrosine kinase.
  465. (2003). Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS.
  466. (1983). Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus.
  467. (2001). Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors.
  468. (1997). Suppression of integrin activation: a novel function of a Ras/Raf-initiated MAP kinase pathway.
  469. (1999). Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP.
  470. (1997). Sustained activation of extracellular-signal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase.
  471. (2004). Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation.
  472. (2005). Systemic delivery of RafsiRNA using cationic cardiolipin liposomes silences Raf-1 expression and inhibits tumor growth in xenograft model of human prostate cancer.
  473. (2006). Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors.
  474. (2000). The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains.
  475. (1993). The cdk2 kinase is required for the G1-to-S transition in mammalian cells.
  476. (1998). The Cell Cycle: A Review. Vet Pathol,
  477. (2001). The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins.
  478. (1987). The complete coding sequence of the human A-raf-1 oncogene and transforming activity of a human A-raf carrying retrovirus.
  479. (1986). The complete coding sequence of the human raf oncogene and the corresponding structure of the c-raf-1 gene.
  480. (1994). The cysteine-rich region of raf-1 kinase contains zinc, translocates to liposomes, and is adjacent to a segment that binds GTP-ras.
  481. (1997). The Drosophila 14-3-3 protein Leonardo enhances Torso signaling through D-Raf in a Ras 1-dependent manner.
  482. (1996). The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases.
  483. (1998). The Eleventh Datta Lecture. The structural basis for substrate recognition and control by protein kinases.
  484. (2006). The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions.
  485. (2000). The hallmarks of cancer.
  486. (1997). The hsp90-binding antibiotic geldanamycin decreases Raf levels and epidermal growth factor signaling without disrupting formation of signaling complexes or reducing the specific enzymatic activity of Raf kinase.
  487. (1994). The ins and outs of Raf kinases.
  488. (2000). The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf.
  489. (2004). The MAP kinase pathway is required for entry into mitosis and cell survival.
  490. (1994). The mitogenactivated protein kinase cascade is activated by B-Raf in response to nerve growth factor through interaction with p21ras.
  491. (1995). The mouse B-raf gene encodes multiple protein isoforms with tissue-specific expression.
  492. (1994). The native structure of the activated Raf protein kinase is a membrane-bound multi-subunit complex.
  493. (1998). The p16INK4a/CDKN2A tumor suppressor and its relatives.
  494. (1994). The p21 inhibitor of cyclindependent kinases controls DNA replication by interaction with PCNA.
  495. (1999). The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts.
  496. (2003). The pro-apoptotic Ras effector
  497. (1998). The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338.
  498. (2004). The RAF proteins take centre stage.
  499. (1990). The Raf-1 kinase as a transducer of mitogenic signals.
  500. (2000). The recruitment of Raf1 to membranes is mediated by direct interaction with phosphatidic acid and is independent of association with Ras.
  501. (1991). The role of Jun, Fos and the AP-1 complex in cellproliferation and transformation.
  502. (1996). The role of the transcription factor Sp1 in regulating the expression of the WAF1/CIP1 gene in U937 leukemic cells.
  503. (1996). The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site.
  504. (1994). The Sos (Son of sevenless) protein.
  505. (1995). The specificity of p53 mutation spectra in sunlight induced human cancers.
  506. (1993). The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain.
  507. (1999). The strength of interaction at the Raf cysteine-rich domain is a critical determinant of response of Raf to Ras family small GTPases.
  508. (1997). The structural basis for 14-3-3:phosphopeptide binding specificity.
  509. (2006). The ubiquitin-proteasome system.
  510. (2000). The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome.
  511. (2001). Themes and variations on ubiquitylation.
  512. (1997). Thrombopoietin-induced differentiation of a human megakaryoblastic leukemia cell line, CMK, involves transcriptional activation of p21(WAF1/Cip1) by STAT5.
  513. (1999). Timing of cyclin E gene expression depends on the regulated association of a bipartite repressor element with a novel E2F complex.
  514. (1995). Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues.
  515. (2006). Towards a lung adenocarcinoma proteome map: studies with SP-C/c-raf transgenic mice.
  516. (1993). Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites
  517. (1996). Transcription factor AP-1 regulation by mitogenactivated protein kinase signal transduction pathways.
  518. (1999). Transcriptional regulation of the p21((WAF1/CIP1)) gene.
  519. (1995). Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions.
  520. (1986). Transgenesis by means of blastocyst-derived embryonic stem cell lines.
  521. (2002). Tumorigenesis: RAF/RAS oncogenes and mismatchrepair status.
  522. (1996). Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation.
  523. (1995). Two distinct Raf domains mediate interaction with Ras.
  524. (2006). Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia.
  525. (1983). Two unrelated cell-derived sequences in the genome of avian leukemia and carcinoma inducing retrovirus MH2.
  526. (2006). Ubiquitin and ubiquitin-like proteins in cancer pathogenesis.
  527. (2000). Understanding Ras: 'it ain't over 'til it's over'.
  528. (2004). Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in vivo: CI-1040 strongly reduces growth and improves lung structure.
  529. (2004). V599EB-RAF is an oncogene in melanocytes.
  530. (1997). WAF1 retards S-phase progression primarily by inhibition of cyclin-dependent kinases.
  531. (1993). WAF1, a potential mediator of p53 tumor suppression.
  532. (1994). WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis.
  533. (2005). Wildtype and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization.
  534. (2008). X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.