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PMID: 7680100 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Redistribution of activated pp60c-src to integrin-dependent cytoskeletal complexes in thrombin-stimulated platelets.

Molecular and cellular biology ·Vol. 13 ·No. 3 ·1993-03-00 ·Pages 1863-71

Clark EA, Brugge JS

Abstract

Thrombin stimulation of platelets induces a transient increase in the specific activity of pp60c-src followed by a redistribution of pp60c-src to the Triton X-100-insoluble, cytoskeleton-rich fraction. Concomitant with the observed increase in pp60c-src activity was a rapid dephosphorylation of tyrosine 527 in 10 to 15% of pp60c-src molecules. In addition, we found that pp60c-src from the Triton-insoluble fraction was phosphorylated on tyrosine 416, the autophosphorylation site which is phosphorylated in activated oncogenic variants of pp60src. Furthermore, in platelets from patients with Glanzmann's thrombasthenia (which are deficient in the integrin receptor GPIIb-IIIa), pp60c-src was not translocated to the Triton-insoluble fraction, and there was a sustained increase in pp60c-src activity following thrombin treatment. These results suggest that pp60c-src is rapidly activated in thrombin-stimulated platelets, potentially by a protein tyrosine phosphatase, before it translocates to a cytoskeletal fraction, where many of its potential substrates are found. The evidence that the cytoskeletal association of pp60c-src is dependent upon engagement of the integrin receptor GPIIb-IIIa suggests that integrin-cytoskeletal complexes may serve to compartmentalize and anchor activated enzymes involved in signal transduction.

MeSH Terms
Biological Transport Cell Compartmentation Cytoskeleton/metabolism Fibrinogen/metabolism Humans Integrins/metabolism Octoxynol Phosphotyrosine Platelet Activation/physiology Platelet Membrane Glycoproteins/metabolism Polyethylene Glycols Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins pp60(c-src)/metabolism Solubility Thrombasthenia/metabolism Thrombin/pharmacology Tyrosine/analogs & derivatives,analysis
Chemicals
Integrins Platelet Membrane Glycoproteins Phosphotyrosine Polyethylene Glycols Tyrosine Fibrinogen Octoxynol Protein-Tyrosine Kinases Proto-Oncogene Proteins pp60(c-src) Thrombin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Clark E A
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Brugge J S
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.3.1863-1871.1993
Published
1993-03-00
Pages
1863-71
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359499
Subset
IM
Grants
NCI NIH HHS · CA08216 · United States
NCI NIH HHS · CA47572 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.3.1863-1871.1993 PMC Full Text View journal details
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