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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IQGAP1 modulates activation of B-Raf
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IQGAP1 modulates activation of B-Raf

机译：IQGAP1调节B-Raf的激活

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IQGAP1 modulates several cellular functions, including cell-cell adhesion, transcription, cytoskeletal architecture, and selected signaling pathways. We previously documented that IQGAP1 binds ERK and MAPK kinase (MEK) and regulates EGF-stimulated MEK and ERK activity. Here we characterize the interaction between IQGAP1 and B-Raf, the molecule immediately upstream of MEK in the Ras/MAPK signaling cascade. B-Raf binds directly to IQGAP1 in vitro and coimmunoprecipitates with IQGAP1 from cell lysates. Importantly, IQGAP1 modulates B-Raf function. EGF is unable to stimulate B-Raf activity in IQGAP1-null cells and in cells transfected with an IQGAP1 mutant construct that is unable to bind B-Raf. Interestingly, binding to IQGAP1 significantly enhances B-Raf activity in vitro. Our data identify a previously unrecognized interaction between IQGAP1 and B-Raf and suggest that IQGAP1 is a scaffold necessary for activation of B-Raf by EGF.
机译：IQGAP1调节几种细胞功能，包括细胞间粘附，转录，细胞骨架结构和选定的信号通路。我们先前已证明IQGAP1结合ERK和MAPK激酶（MEK）并调节EGF刺激的MEK和ERK活性。在这里，我们描述了IQGAP1和B-Raf之间的相互作用，B-Raf是Ras / MAPK信号级联反应中MEK紧邻的上游分子。 B-Raf在体外直接与IQGAP1结合，并与来自细胞裂解液的IQGAP1共免疫沉淀。重要的是，IQGAP1调节B-Raf功能。 EGF无法刺激IQGAP1无效细胞和被无法结合B-Raf的IQGAP1突变体构建体转染的细胞中的B-Raf活性。有趣的是，与IQGAP1的结合在体外显着增强了B-Raf的活性。我们的数据确定了IQGAP1和B-Raf之间以前无法识别的相互作用，并表明IQGAP1是EGF激活B-Raf所必需的支架。

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