Article Text

  1. J. Profirovic,
  2. J. Niu,
  3. M. Gorovoy,
  4. T. Voyno-Yasenetskaya
  1. College of Medicine, University of Illinois


Vasodilator-stimulated phosphoprotein (VASP) is actively involved in regulation of actin cytoskeleton dynamics and cell motility. VASP phosphorylation diminishes its actin nucleation and polymerization activities, thus serving as a negative regulator for actin polymerization. Here we show that in human umbilical vein endothelial cells (HUVEC) α-thrombin induced VASP phosphorylation that was mediated, at least in part, via alpha subunit of heterotrimeric G13. Moreover, we described a novel mechanism of Gα13-induced cAMP-independent PKA activation. We show that α-thrombin and Gα13-induced VASP phosphorylation is inhibited by a specific PKA inhibitor 14-22 amide and H-89. Importantly, α-thrombin stimulation and expression of activated Gα13 did not induce cAMP production over the basal level, suggesting that VASP phosphorylation is the result of cAMP-independent PKA activation. Gα13-dependent VASP phosphorylation may also be inhibited by a specific Rho inhibitor botulinum toxin C3 and by a dominant negative mutant of MEKK1. In addition, expression of phosphorylation deficient IκB and pretreatment with proteasome inhibitor MG-132 abolished Gα13- and α-thrombin-induced VASP phosphorylation, respectively. In summary, we have described a novel pathway of Gα13-induced VASP phosphorylation that involves activation of RhoA and MEKK1, phosphorylation and degradation of IκB, release of PKA catalytic subunit from the complex with IκB and NFκB and subsequent phosphorylation of VASP. Research founded by National Institutes of Health grants GM56159 and GM65160 and American Heart Association (AHA) grant to T.V.-Y., AHA predoctoral fellowship 0310030Z to J.P.

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.