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MBC in Press, published online ahead of print August 31, 2005
Mol. Biol. Cell 10.1091/mbc.E05-03-0263

A more recent version of this article appeared on November 1, 2005
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Submitted on March 30, 2005
Revised on August 18, 2005
Accepted on August 19, 2005

Divergent Roles of c-Src in Controlling PDGF-dependent Signaling in Fibroblasts

Kavita Shah and Fabien Vincent*

Department of Chemistry, Purdue University, West Lafayette, IN 47907

Monitoring Editor: David Drubin

The vast complexity of PDGF-induced downstream signaling pathways is well known, but the precise roles of critical players still elude us due to our lack of specific and temporal control over their activities. Accordingly, while Src family members are some of the better characterized effectors of PDGF{beta} signaling, considerable controversy still surrounds their precise functions. To address these questions and limitations, we applied a chemical-genetic approach to study the role of c-Src at the cellular level, in defined signaling cascades, uncovered novel phosphorylation targets and defined its influence on transcriptional events. The spectacular control of c-Src on actin reorganization and chemotaxis was delineated by global substrate labeling and transcriptional analysis, revealing multiple cytoskeletal proteins and chemotaxis promoting genes to be under c-Src control. Additionally, this tool revealed the contrasting roles of c-Src in controlling DNA synthesis, where it transmits conflicting inputs via the PI3K and Ras pathways. Finally, this study reveals a mechanism by which SFKs may control PDGF mediated responses both at transcriptional and translational levels.

*Present address: Renovis, 2 Corporate Drive, South San Francisco, CA 94080.

Address correspondence to: Kavita Shah (shah23{at}purdue.edu)




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