Affordable Access

deepdyve-link deepdyve-link
Publisher Website

Hematopoietic lineage cell-specific protein-1 (HS1) regulates PAR-mediated ERK activation and thromboxane generation in platelets.

Authors
  • Kahner, Bryan N
  • Dorsam, Robert T
  • Kim, Soochong
  • Shankar, Haripriya
  • Kitamura, Daisuke
  • Kunapuli, Satya P
Type
Published Article
Journal
Platelets
Publisher
Informa UK (Taylor & Francis)
Publication Date
Dec 01, 2008
Volume
19
Issue
8
Pages
614–623
Identifiers
DOI: 10.1080/09537100802351057
PMID: 19012179
Source
Medline
License
Unknown

Abstract

Thrombin-induced platelet activation leads to tyrosine phosphorylation of hematopoietic lineage cell-specific protein-1 (HS1), a 75 kDa adapter protein expressed exclusively in cells of hematopoietic lineage. We have shown HS1 to be a functionally important signaling molecule downstream of PAR-4 and GPVI collagen receptor. We have thus begun to elucidate PAR signaling pathway of HS1 phosphorylation, and its functional implications. PAR-1 and PAR-4 activating peptides (SFLLRN and AYPGKF, respectively) induced HS1 phosphorylation in a Gq-dependent manner as shown by incubation with the Gq inhibitor, YM254890. Consistently, HS1 phosphorylation was abolished in platelets from Gq deficient mice upon AYPGKF stimulation. Treatment with ADP receptor antagonists did not affect HS1 phosphorylation. Pretreatment of platelets with Src kinase inhibitors abolished HS1 phosphorylation. Further Syk activation, as measured by tyrosine phosphorylation of Syk (residues 525/526), in response to PAR activation was abolished in the presence of Src inhibitors. HS1 null mice show inhibition of PAR-mediated thromboxane A2 generation compared to wild type littermates. Phosphorylation of Erk, a key signaling molecule in thromboxane generation, was also diminished in HS1 null mice platelets. Based on these findings, we conclude that tyrosine phosphorylation of HS1 occurs downstream of both PAR-1 and PAR-4. HS1 phosphorylation is a Gq mediated response regulated by Src kinases. Thus, HS1 may mediate PAR-induced thromboxane generation through regulation of Erk phosphorylation.

Report this publication

Statistics

Seen <100 times