VASP (vasodilator-stimulated phosphoprotein) is an actin- and profilin-binding protein that is expressed in platelets at high levels and plays a major role in negatively regulating secretory and adhesive events in these cells. VASP is a major substrate for cAMP- and cGMP-regulated protein kinases and it has been shown to be directly phosphorylated on Ser157 by PKC (protein kinase C). In the present paper, we show that, in human platelets, VASP is phosphorylated by PKC on Ser157, but not Ser239, in response to phorbol ester stimulation, in a manner blocked by the PKC inhibitor BIM I (bisindolylmaleimide I). In response to thrombin, VASP was also phosphorylated on Ser157, but this response was only partially inhibited by BIM I, indicating PKC-dependent and -independent pathways to VASP phosphorylation by thrombin. Using inhibitors, we have ruled out the possibility that the PKC-independent pathway acts through guanylate cyclase generation of cGMP, or through a phosphoinositide 3-kinase-dependent kinase. Inhibition of Rho kinase, however, substantially reduced Ser157 VASP phosphorylation, and its effects were additive with BIM I. This implicates Rho kinase and PKC as the major kinases that phosphorylate VASP Ser157 in response to thrombin in platelets.
Skip Nav Destination
Article navigation
January 2006
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
December 23 2005
Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser157 by protein kinase C-dependent and -independent mechanisms in thrombin-stimulated human platelets
James K. T. Wentworth;
James K. T. Wentworth
1Department of Pharmacology, School of Medical Sciences, University Walk, Bristol BS8 1TD, U.K.
Search for other works by this author on:
Giordano Pula;
Giordano Pula
1Department of Pharmacology, School of Medical Sciences, University Walk, Bristol BS8 1TD, U.K.
Search for other works by this author on:
Alastair W. Poole
Alastair W. Poole
1
1Department of Pharmacology, School of Medical Sciences, University Walk, Bristol BS8 1TD, U.K.
1To whom correspondence should be addressed (email a.poole@bris.ac.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 13 2005
Revision Received:
September 26 2005
Accepted:
October 03 2005
Accepted Manuscript online:
October 03 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 393 (2): 555–564.
Article history
Received:
May 13 2005
Revision Received:
September 26 2005
Accepted:
October 03 2005
Accepted Manuscript online:
October 03 2005
Citation
James K. T. Wentworth, Giordano Pula, Alastair W. Poole; Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser157 by protein kinase C-dependent and -independent mechanisms in thrombin-stimulated human platelets. Biochem J 15 January 2006; 393 (2): 555–564. doi: https://doi.org/10.1042/BJ20050796
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.