Late signaling in the activated platelets upregulates tyrosine phosphatase SHP1 and impairs platelet adhesive functions: regulation by calcium and Src kinase

Gupta, Ramkrishna ; Chakrabarti, Partha ; Dikshit, Madhu ; Dash, Debabrata (2007) Late signaling in the activated platelets upregulates tyrosine phosphatase SHP1 and impairs platelet adhesive functions: regulation by calcium and Src kinase Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1773 (2). pp. 131-140. ISSN 0167-4889

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/j.bbamcr.2006.08.055

Abstract

Sustained stimulation of platelets with protease-activated receptor agonists in presence of extracellular calcium was associated with tyrosine dephosphorylation of specific proteins of relative mobilities 35, 67, and 75 kDa. From phosphatase assays and inhibitor studies SHP1, a Src homology 2 (SH2) domain-containing tyrosine phosphatase expressed abundantly in hemopoietic cells, was found to be upregulated in platelets between 25 and 30 min following thrombin stimulation. Concomitantly, SHP1 was tyrosine phosphorylated by, and coprecipitated with, Src tyrosine kinase. SHP1 activation, association with Src and dephosphorylation of specific proteins were dependent on extracellular calcium and maintenance of a higher cytosolic calcium plateau. There was progressive impairment of platelet functions like aggregability and clot retraction, associated with downregulation of fibrinogen-binding affinity of integrin αIIbβ3, in the platelets exposed to thrombin for 45 min. This could reflect the late physiological changes in platelets when the cells are consistently exposed to stimulatory signals under thrombogenic environment in vivo.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Platelet Activation; Intracellular Calcium; Protein Tyrosine Phosphatase; Src Tyrosine Kinase; SHP1; Thrombin
ID Code:89075
Deposited On:30 Mar 2012 10:38
Last Modified:30 Mar 2012 10:38

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