Crk-associated substrate,vascular smooth muscle and hypertension

Hypertension is characterized by vascular smooth muscle constriction and vascular remodeling involving cell migration,hypertrophy and growth.Crk-associated substrate(CAS),the first discovered member of the adapter protein CAS family,has been shown to be a critical cellular component that regulates various smooth muscle functions.In this review,the molecular structure and protein interactions of the CAS family members are summarized.Evidence for the role of CAS in the regu-lation of vascular smooth muscle contractility is pre-sented.Contraction stimulation induces CAS phosphor-ylation on Tyr-410 in arterial smooth muscle,creating the binding site for the Src homology(SH)2/SH3 protein CrkII,which activates neuronal Wiskott-Aldrich syn-drome protein(N-WASP)-mediated actin assembly and force development.The functions of CAS in cell migra-tion,hypertrophy and growth are also summarized.Abelson tyrosine kinase(Abl),c-Src,focal adhesion kinase(FAK),proline-rich tyrosine kinase 2(PYK2),pro-tein tyrosine phosphatase-proline,glutamate,serine and threonine sequence protein(PTP-PEST)and SHP-2 have been documented to coordinate the phosphorylation and dephosphorylation of CAS.The downstream signaling partners of CAS in the context of cell motility,hyper-trophy,survival and growth are also discussed.These new findings establish the important role of CAS in the modulation of vascular smooth muscle functions.Furthermore,the upstream regulators of CAS may be new biologic targets for the development of more effective and specific treatment of cardiovascular diseases such as hypertension.