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Molecular and Cellular Biology, June 2006, p. 4399-4409, Vol. 26, No. 12
0270-7306/06/$08.00+0     doi:10.1128/MCB.01147-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Src SH2 Arginine 175 Is Required for Cell Motility: Specific Focal Adhesion Kinase Targeting and Focal Adhesion Assembly Function{dagger}

Myeong Gu Yeo,{ddagger} Michael A. Partridge,{ddagger} Ellen J. Ezratty, Qiong Shen, Gregg G. Gundersen, and Eugene E. Marcantonio*

Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York 10032

Received 20 June 2005/ Returned for modification 30 August 2005/ Accepted 30 March 2006

Src kinase is a crucial mediator of adhesion-related signaling and motility. Src binds to focal adhesion kinase (FAK) through its SH2 domain and subsequently activates it for phosphorylation of downstream substrates. In addition to this binding function, data suggested that the SH2 domain might also perform an important role in targeting Src to focal adhesions (FAs) to enable further substrate phosphorylations. To examine this, we engineered an R175L mutation in cSrc to prevent the interaction with FAK pY397. This constitutively open Src kinase mediated up-regulated substrate phosphorylation in SYF cells but was unable to promote malignant transformation. Significantly, SrcR175L cells also had a profound motility defect and an impaired FA generation capacity. Importantly, we were able to recapitulate wild-type motile behavior and FA formation by directing the kinase to FAs, clearly implicating the SH2 domain in recruitment to FAK and indicating that this targeting capacity, and not simply Src-FAK scaffolding, was critical for normal Src function.

* Corresponding author. Mailing address: Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032. Phone: (212) 305-1148. Fax: (212) 305-5498. E-mail: eem2{at}columbia.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this work.

Molecular and Cellular Biology, June 2006, p. 4399-4409, Vol. 26, No. 12
0270-7306/06/$08.00+0     doi:10.1128/MCB.01147-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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  • Partridge, M. A., Marcantonio, E. E. (2006). Initiation of Attachment and Generation of Mature Focal Adhesions by Integrin-containing Filopodia in Cell Spreading. Mol. Biol. Cell 17: 4237-4248 [Abstract] [Full Text]  


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