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J. Biol. Chem., Vol. 282, Issue 40, 29122-29129, October 5, 2007

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Src Family Kinases Promote Vessel Stability by Antagonizing the Rho/ROCK Pathway^*

From the Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114

Src family kinases (SFKs) are one of the signaling enzymes that contribute to angiogenesis, but their precise input to the various phases of the angiogenic program has not been defined. Using an in vitro model system, we discovered that SFKs promoted the formation of tubes and prevented their regression. They suppressed regression by activating the ERK pathway that antagonized the Rho/ROCK pathway, which was essential for regression. These studies reveal that SFKs contribute to several phases of the angiogenic program and identify the downstream effectors by which SFKs stabilize tubes.

Received for publication, March 27, 2007 , and in revised form, July 31, 2007.

^* This work was supported by a Young Clinical Scientist award from Flight Attendant Medical Research Institute (to E. I.) and National Institutes of Health Grant EY016385 (to A. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Materials and Methods and Figs. S1–S4.

¹ To whom correspondence should be addressed: Schepens Eye Research Institute, Harvard Medical School, 20 Staniford St., Boston, MA 02114. Tel.: 617-912-2517; Fax: 617-912-0111; E-mail: ak{at}eri.harvard.edu.

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