COLLAGEN INDUCES TYROSINE PHOSPHORYLATION OF WISKOTT-ALDRICH-SYNDROMEPROTEIN IN HUMAN PLATELETS

Citation
A. Oda et al., COLLAGEN INDUCES TYROSINE PHOSPHORYLATION OF WISKOTT-ALDRICH-SYNDROMEPROTEIN IN HUMAN PLATELETS, Blood, 92(6), 1998, pp. 1852-1858
Citations number
49
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
92
Issue
6
Year of publication
1998
Pages
1852 - 1858
Database
ISI
SICI code
0006-4971(1998)92:6<1852:CITPOW>2.0.ZU;2-P
Abstract
Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are caused by mutations of the WAS protein (WASP) gene. All hematopoietic stem cell-derived lineages, including platelets, express WASP. Platel ets from WAS patients are smaller than their normal counterparts and d efects in platelet aggregation and actin polymerization have been repo rted. To determine if WASP is important for normal platelet function, we examined its role in signal transduction. We found that collagen bu t not thrombopoietin or thrombin induces a rapid and robust increase i n tyrosine phosphorylation of platelet-associated WASP. Collagen-induc ed tyrosine phosphorylation of WASP was inhibited by cytochalasin D an d wortmannin. respectively, suggesting that actin polymerization and p hosphatidylinositol 3-kinase (Pla-kinase) play a role in the induction of tyrosine phosphorylation of WASP. Binding of glutathion S-transfer ase (GST)Grb2 to WASP was seen in the lysate of resting platelets. The binding was reduced when lysates from collagen-stimulated platelets w ere incubated with GST-Grb2, suggesting that tyrosine phosphorylation of WASP may directly or indirectly modulate the adapter function of WA SP. Although thrombin- and thrombopoietin-induced increase in tyrosine phosphorylation of WASP is negligible or marginal, WASP from thrombin -activated platelets became incorporated into the Triton X-100-insolub le 10,000g sedimentable residue in an aggregation-dependent manner, su ggesting that it may have a regulatory role in platelet cytoskeletal p rocesses during aggregation. Lastly. we found that WASP is cleaved in response to activation of calpain, a protease that may have a role in postaggregation signaling processes. Our data suggest that collagen sp ecifically induces an increase in tyrosine phosphorylation of WASP and that WASP is involved in signaling during thrombin-induced aggregatio n by its redistribution to the cytoskeleton and its cleavage during ag gregation. (C) 1998 by The American Society of Hematology.