Abstract 17323: Regulation of Vascular Smooth Muscle Cell Migration and Phenotype by the Neuronal Repellent Slit
Slit is a recently discovered, secreted protein that regulates neuronal cell guidance by activating its cognate receptor Roundabout (Robo). The slit-robo-GTPase Activating Protein (srGAP) is among the proteins recruited by Robo upon Slit activation, and srGAP regulates the activity of the Rho family of small GTPases by promoting their GTP hydrolysis. We initially studied how protein phosphorylation by protein kinase A (PKA) regulates growth and differentiation of vascular smooth muscle cells (VSMC). Through a phospho-proteomics search for novel substrates of PKA, we identified srGAP1 as a major novel PKA target in VSMC. However, the function of Slit-Robo-srGAP signaling in VSMC was not previously investigated. In this study, we show that Robo1 and srGAP1 are abundant in VSMC and their expression is significantly increased in ligation-induced neointima of mouse carotid arteries. In cultured VSMC, Slit inhibited migration as well smooth muscle gene expression of VSMC through regulation of Rho small GTPases and of serum response factor SRF.
- © 2010 by American Heart Association, Inc.