2,297 research outputs found

    PCN39 TREATMENT PATTERNS AMONG PATIENTS WITH ADVANCED MELANOMA:A RETROSPECTIVE LONGITUDINAL STUDY

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    Pericas, Enri

    Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2

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    The Ras oncogene products regulate the expression of genes in transformed cells, and members of the Ets family of transcription factors have been implicated in this process. To determine which Ets factors are the targets of Ras signaling pathways, the abilities of several Ets factors to activate Ras-responsive enhancer (RRE) reporters in the presence of oncogenic Ras were examined. In transient transfection assay, reporters containing RREs composed of Ets-AP-1 binding sites could be activated 30-fold in NIH 3T3 fibroblasts and 80-fold in the macrophage-like line RAW264 by the combination of Ets1 or Ets2 and Ras but not by several other Ets factors that were tested in the assay. Ets2 and Ras also superactivated an RRE composed of Ets-Ets binding sites, but the Ets-responsive promoter of the c-fms gene was not superactivated. Mutation of a threonine residue to alanine in the conserved amino-terminal regions of Ets1 and Ets2 (threonine 38 and threonine 72, respectively) abrogated the ability of each of these proteins to superactivate reporter gene expression. Phosphoamino acid analysis of radiolabeled Ets2 revealed that Ras induced normally absent threonine-specific phosphorylation of the protein. The Ras-dependent increase in threonine phosphorylation was not observed in Ets2 proteins that had the conserved threonine 72 residue mutated to alanine or serine. These data indicate that Ets1 and Ets2 are specific nuclear targets of Ras signaling events and that phosphorylation of a conserved threonine residue is a necessary molecular component of Ras-mediated activation of these transcription factors

    Spin dynamics and disorder effects in the S=1/2 kagome Heisenberg spin liquid phase of kapellasite

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    We report 35^{35}Cl NMR, ESR, μ\muSR and specific heat measurements on the S=1/2S=1/2 frustrated kagom\'e magnet kapellasite, α\alpha-Cu3_3Zn(OH)6_6Cl2_2, where a gapless spin liquid phase is stabilized by a set of competing exchange interactions. Our measurements confirm the ferromagnetic character of the nearest-neighbour exchange interaction J1J_1 and give an energy scale for the competing interactions J10|J| \sim 10 K. The study of the temperature-dependent ESR lineshift reveals a moderate symmetric exchange anisotropy term DD, with D/J3|D/J|\sim 3%. These findings validate a posteriori the use of the J1J2JdJ_1 - J_2 - J_d Heisenberg model to describe the magnetic properties of kapellasite [Bernu et al., Phys. Rev. B 87, 155107 (2013)]. We further confirm that the main deviation from this model is the severe random depletion of the magnetic kagom\'e lattice by 27%, due to Cu/Zn site mixing, and specifically address the effect of this disorder by 35^{35}Cl NMR, performed on an oriented polycrystalline sample. Surprisingly, while being very sensitive to local structural deformations, our NMR measurements demonstrate that the system remains homogeneous with a unique spin susceptibility at high temperature, despite a variety of magnetic environments. Unconventional spin dynamics is further revealed by NMR and μ\muSR in the low-TT, correlated, spin liquid regime, where a broad distribution of spin-lattice relaxation times is observed. We ascribe this to the presence of local low-energy modes.Comment: 15 pages, 11 figures. To appear in Phys. Rev.
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