Bruton's tyrosine kinase is a substrate of calpain in human platelets.
Platelet-associated Bruton's tyrosine kinase (Btk) was completely cleaved if treated with calcium ionophore A23187 with appearance of a proteolytic product of 27 kDa size. Aggregation with thrombin also induced about 10% degradation of Btk after 30 min. Calpain inhibitors prevented Btk degradation in both. The proteolytic products of the Wiskott-Aldrich syndrome protein (WASP), a calpain and Btk substrate, and the 27 kDa degradation product of Btk did not redistribute to the Triton-insoluble cytoskeleton in thrombin-aggregated platelets, in contrast to the uncleaved proteins. The degradation of Btk and WASP was independent of their tyrosine phosphorylation status. These results indicate that Btk is an endogenous substrate for calpain, the cleavage of which may have functional consequences in long-term post-aggregation events in platelets.
Mukhopadhyay
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S
Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Ramars
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AS
Ochs
H D
HD
Dash
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D
D000077329:Agammaglobulinaemia Tyrosine Kinase; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004151:Dipeptides / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D017830:Octoxynol / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D051316:Wiskott-Aldrich Syndrome Protein
D004151:Dipeptides; D007476:Ionophores; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; C071482:calpeptin; D000001:Calcimycin; D017830:Octoxynol; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D013917:Thrombin; D002154:Calpain; D002118:Calcium