Bruton's tyrosine kinase associates with the actin-based cytoskeleton in activated platelets.
Bruton's tyrosine kinase (Btk) plays a crucial role in the maturation and differentiation of B-lymphocytes and immunoglobulin synthesis. Recently Btk has been described to be present in significant amount in human platelets. To investigate the regulation of this kinase in the platelets we studied its subcellular redistribution in the resting and activated cells. In the resting platelets Btk was almost absent from the actin-based cytoskeleton. Upon challenge of the platelet thrombin receptor upto 30% of total Btk appeared in the cytoskeleton and the protein underwent phosphorylation on tyrosine. Translocation of Btk to the cytoskeleton but not aggregation was prevented by cytochalasin B, which inhibits actin polymerization. Wortmannin and genistein (inhibitors of phosphoinositide 3-kinase and protein tyrosine kinase, respectively) decreased while phenylarsine oxide (a tyrosine phosphatase inhibitor) increased the cytoskeletal content of Btk. The association of Btk with the cytoskeleton was regulated by integrin alpha(IIb)beta(3) and partly reversible. Taken together, these data suggest that Btk might be a component of a signaling complex containing specific cytoskeletal proteins in the activated platelets.
Mukhopadhyay
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Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi -221005, India.
Ramars
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AS
Dash
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D000199:Actins / Q000737:chemistry; D000077329:Agammaglobulinaemia Tyrosine Kinase; D015703:Antigens, CD / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology / Q000201:enzymology*; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D018179:Receptors, Thrombin / Q000378:metabolism*
D000199:Actins; D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017452:Receptors, IgG; D018179:Receptors, Thrombin; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D010744:Phosphoric Monoester Hydrolases