Important role of Abelson tyrosine kinase (Abl) in regulating vascular smooth muscle contraction

Abstract

There is emerging evidence that the actin cytoskeleton is involved in diverse array of pathways leading to vascular smooth muscle (VSM) contraction. Among the protein kinases participating in actin rearrangement, Abl is known for its ability to bind directly to F-actin. However, Abl implication in VSM excitation-contraction coupling remains unclear. This study elucidates the role of Abl in the contractions of vascular smooth muscle rings (VSMR) from the rat mesenteric artery. VSMR stimulation with norepinephrine (NE) initiated phosphorylation of Abl at Tyr-245 and Tyr-412 (indication of Abl activation) and the putative Abl downstream molecule p130 Crk-associated substrate (CAS) phosphorylation on Tyr-410. To silence gene expression, Abl shRNA was introduced into VSMR by reversible permeabilization plus liposomes and the rings were incubated for two days allowing Abl to degrade. Immunoblot showed lower Abl expression in shRNA-treated rings. The treatment with shRNA attenuated NE-induced contractions and the increase in F-actin/G-actin ratios. Abl downexpression affected NE-induced phosphorylation of CAS known to regulate active force generation in smooth muscle. Our study shows for the first time that Abl plays an important role in the regulation of VSM contraction. CAS phosphorylation may be a downstream mechanism of the Abl-associated pathway. Supported by NIH HL-75388