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BIOLOGICAL SCIENCES / CELL BIOLOGY
IQGAP1 modulates activation of B-Raf

Jian-Guo Ren, Zhigang Li, and David B. Sacks^*

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115

Edited by Robert J. Lefkowitz, Duke University Medical Center, Durham, NC, and approved May 17, 2007 (received for review December 19, 2006)

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.

EGF | MAP kinase | signalling

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0611308104/DC1.

*To whom correspondence should be addressed at: Brigham and Women's Hospital, Thorn 530, 75 Francis Street, Boston, MA 02115. E-mail: dsacks{at}rics.bwh.harvard.edu

© 2007 by The National Academy of Sciences of the USA

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