Abl knockout differentially affects p130 Crk-associated substrate, vinculin, and paxillin in blood vessels of mice

AUTOR(ES)

Chen, Shu

FONTE

American Physiological Society

RESUMO

Actin polymerization has recently emerged as an important cellular process that regulates smooth muscle contraction. Abelson tyrosine kinase (Abl) has been implicated in the regulation of actin dynamics and force development in vascular smooth muscle. In the present study, the systolic blood pressure was lower in Abl−/− knockout mice compared with wild-type mice. The knockout of Abl diminished the tyrosine phosphorylation of p130 Crk-associated substrate (CAS, an adapter protein associated with smooth muscle contraction) in resistance arteries upon stimulation with phenylephrine or angiotensin II. The agonist-elicited enhancement of F-actin-to-G-actin ratios in arteries assessed by fluorescent microscopy was also reduced in Abl−/− mice. It has been known that vinculin is a structural protein that links actin filaments to extracellular matrix via transmembrane integrins, whereas paxillin is a signaling protein associated with focal contacts mediating actin cytoskeleton remodeling. The expression of vinculin and paxillin at protein and messenger levels was lower in arterial vessels from Abl knockout mice. However, the agonist-induced increase in myosin phosphorylation was not attenuated in arteries from Abl knockout mice. These results indicate that Abl differentially regulates Crk-associated substrate, vinculin, and paxillin in arterial vessels. The Abl-regulated cellular process and blood pressure are independent of myosin activation in vascular smooth muscle.

Documentos Relacionados

• CrkII regulates focal adhesion kinase activation by making a complex with Crk-associated substrate, p130Cas
• Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas.
• Paxillin α and Crk-associated substrate exert opposing effects on cell migration and contact inhibition of growth through tyrosine phosphorylation
• The Integrin β1 Subunit Transmembrane Domain Regulates Phosphatidylinositol 3-Kinase-dependent Tyrosine Phosphorylation of Crk-associated Substrate
• A p130Cas tyrosine phosphorylated substrate domain decoy disrupts v-Crk signaling