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Kank attenuates actin remodeling by preventing interaction between IRSp53 and Rac1

By Badal Chandra Roy, Naoto Kakinuma and Ryoiti Kiyama


In this study, insulin receptor substrate (IRS) p53 is identified as a binding partner for Kank, a kidney ankyrin repeat–containing protein that functions to suppress cell proliferation and regulate the actin cytoskeleton. Kank specifically inhibits the binding of IRSp53 with active Rac1 (Rac1G12V) but not Cdc42 (cdc42G12V) and thus inhibits the IRSp53-dependent development of lamellipodia without affecting the formation of filopodia. Knockdown (KD) of Kank by RNA interference results in increased lamellipodial development, whereas KD of both Kank and IRSp53 has little effect. Moreover, insulin-induced membrane ruffling is inhibited by overexpression of Kank. Kank also suppresses integrin-dependent cell spreading and IRSp53-induced neurite outgrowth. Our results demonstrate that Kank negatively regulates the formation of lamellipodia by inhibiting the interaction between Rac1 and IRSp53

Topics: Research Articles
Publisher: The Rockefeller University Press
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    1. (1995). A conserved binding motif defi nes numerous candidate target proteins for both Cdc42 and Rac GTPases.
    2. (2003). A differential genomic cloning for cancer study: an outline and applications. Recent Research Developments
    3. (2004). A novel actin bundling/fi lopodium-forming domain conserved in insulin receptor tyrosine kinase substrate p53 and missing in metastasis protein.
    4. (2002). A novel ankyrin repeat-containing gene (Kank) located at 9p24 is a growth suppressor of renal cell carcinoma.
    5. (2004). Abi1 is essential for the formation and activation of a WAVE2 signalling complex.
    6. (2000). Activation by
    7. (2001). An effector region in Eps8 is responsible for the activation of the Rac-specifi c GEF activity of Sos-1 and for the proper localization of the Rac-based actinpolymerizing machine.
    8. (2004). An endoribonuclease-prepared siRNA screen in human cells identifi es genes essential for cell division.
    9. (1999). Bjarneg å rd
    10. (2003). C. elegans ankyrin repeat protein VAB-19 is a component of epidermal attachment structures and is essential for epidermal morphogenesis.
    11. (2001). Cdc42 induces fi lopodia by promoting the formation of an IRSp53:Mena complex.
    12. (2001). Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing the 58-kD insulin receptor substrate to fi lamentous actin.
    13. (2003). Cell migration: integrating signals from front to back.
    14. (2001). Coiled coils: a highly versatile protein folding motif.
    15. (1999). Dentatorubralpallidoluysian atrophy protein interacts through a proline-rich region near polyglutamine with the SH3 domain of an insulin receptor tyrosine kinase substrate
    16. (1999). Effectors for the Rho GTPases.
    17. (2007). Ena/VASP proteins have an anti-capping independent function in fi lopodia formation.
    18. (2005). F ü tterer .
    19. For transfection, after cells were grown to 80 – 90% confl uency, they were
    20. (2004). Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD-95.
    21. (1998). Integrin-mediated signals regulated by members of the rho family of GTPases.
    22. (2002). Integrins: bidirectional allosteric signaling machines.
    23. (2003). IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and fi lopodia independently of Mena.
    24. (2004). IRSp53/Eps8 complex is important for positive regulation of Rac and cancer cell motility/invasiveness. Cancer Res.
    25. (1997). Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth.
    26. (2008). Kank regulates RhoA-dependent formation of actin stress fi bers and cell migration via 14-3-3 in PI3K – Akt signaling.
    27. (2001). Kinectin is a key effector of RhoG microtubule-dependent cellular activity.
    28. (2002). Mechanism of regulation of WAVE1-induced actin nucleation by
    29. (2005). NMDA receptor-dependent synaptic translocation of insulin receptor substrate p53 via protein kinase C signaling.
    30. (2005). Pathological characterization of Kank in renal cell carcinoma.
    31. (2002). Phosphatidylinositol 4-phosphate 5-kinase is essential for ROCK-mediated neurite remodeling.
    32. (2003). Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1.
    33. (2007). Pyk ä l ä inen
    34. (1994). rac p21 is involved in insulin-induced membrane ruffl ing and rho p21 is involved in hepatocyte growth factor- and 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced membrane ruffl ing in KB cells.
    35. Regulation of cell shape by Cdc42 is mediated by the synergic actinbundling activity of the
    36. (2005). Regulation of dendritic spine morphogenesis by insulin receptor substrate 53, a downstream effector of Rac1 and Cdc42 small GTPases.
    37. (2004). Regulation of WASP/WAVE proteins: making a long story short.
    38. (2004). Rho and Rac take center stage.
    39. (1997). Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1 and acetylcholine and collapse induced by RhoA and lysophosphatidic acid.
    40. (1997). Rho GTPases and signaling networks.
    41. (1998). Rho GTPases and the actin cytoskeleton.
    42. (2002). Rho GTPases in cell biology.
    43. (2000). Rho GTPases in neuronal morphogenesis.
    44. (2002). Short RNA duplexes produced by hydrolysis with Escherichia coli RNase III mediate effective RNA interference in mammalian cells.
    45. (2007). Structural basis for the actin-binding function of missing-in-metastasis.
    46. (1999). The ankyrin repeat: a diversity of interactions on a common structural framework.
    47. (1996). The GTPase-activating protein n-chimaerin cooperates with Rac1 and Cdc42Hs to induce the formation of lamellipodia and fi lopodia.
    48. (2006). The RAC binding domain/IRSp53-MIM homology domain of IRSp53 induces RAC-dependent membrane deformation.
    49. (1995). The Ras related protein Cdc42Hs and bradykinin promote formation of peripheral actin micro spikes and fi lopodia in Swiss 3T3 fi broblasts.
    50. (1992). The small GTP-binding protein rac regulates growth factor-induced membrane ruffl ing.
    51. (2005). Tiam1-IRSp53 complex formation directs specifi city of rac-mediated actin cytoskeleton regulation.
    52. (2004). to actin assembly driving lamellipodia formation.
    53. (2001). WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin fi laments and cell movement.
    54. (2002). WAVE2 serves a functional partner of IRSp53 by regulating its interaction with Rac.

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