IQGAP1调节B-Raf的激活。
IQGAP1 modulates activation of B-Raf.
作者信息
Ren Jian-Guo, Li Zhigang, Sacks David B
机构信息
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
出版信息
Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10465-9. doi: 10.1073/pnas.0611308104. Epub 2007 Jun 11.
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.
IQGAP1调节多种细胞功能，包括细胞间粘附、转录、细胞骨架结构以及特定的信号通路。我们之前记录到IQGAP1与ERK和丝裂原活化蛋白激酶激酶（MEK）结合，并调节表皮生长因子（EGF）刺激的MEK和ERK活性。在此，我们描述了IQGAP1与B-Raf之间的相互作用，B-Raf是Ras/丝裂原活化蛋白激酶（MAPK）信号级联中MEK的直接上游分子。B-Raf在体外直接与IQGAP1结合，并与来自细胞裂解物的IQGAP1进行共免疫沉淀。重要的是，IQGAP1调节B-Raf的功能。在IQGAP1基因敲除细胞和转染了无法与B-Raf结合的IQGAP1突变构建体的细胞中，EGF无法刺激B-Raf活性。有趣的是，在体外与IQGAP1结合可显著增强B-Raf活性。我们的数据确定了IQGAP1与B-Raf之间一种先前未被认识到的相互作用，并表明IQGAP1是EGF激活B-Raf所必需的支架蛋白。
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