title: Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets.
abstract: Tec is a non-receptor type tyrosine kinase which is tyrosine phosphorylated and activated upon stimulation of hematopoietic cells with various cytokines. The role of Tec in G protein-coupled receptor- and integrin-mediated signalings has not been elucidated. We therefore investigated the regulation of Tec in human blood platelets. Tec was rapidly tyrosine phosphorylated in response to platelet agonists which activate G protein-coupled receptors such as thromboxane A2 analog (U46619), thrombin, and thrombin receptor activating peptide (TRAP). TRAP-induced phosphorylation in Tec was significantly reduced under the conditions which abrogate fibrinogen binding to GP IIb-IIIa and subsequent platelet aggregation. However, TRAP induced significant levels of the phosphorylation even under these conditions and also in thrombasthenic platelets which lack functional GP IIb-IIIa molecules, suggesting that activation of G-protein-coupled receptor causes the phosphorylation. To clarify whether integrin engagement by itself causes the phosphorylation in Tec, we examined the state of the phosphorylation in platelets activated by integrin engagement. Platelet adhesion to immobilized fibrinogen or collagen induced significant levels of the phosphorylation. Furthermore, Tec was translocated to cytoskeleton in response to TRAP in a manner dependent on platelet aggregation, suggesting that Tec can be a component of integrin-mediated signalings. These results collectively indicate that Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets.
authors.affiliation: Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hamazaki
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: H
authors.initials: H
authors.lastname: Mano
authors.forename: Y
authors.initials: Y
authors.lastname: Nagata
authors.forename: K
authors.initials: K
authors.lastname: Todokoro
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: T
authors.initials: T
authors.lastname: Nagasawa
mesh_terms: D000199:Actins / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000097:blood*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011108:Polymers; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000199:Actins; D016023:Integrins; D008024:Ligands; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011108:Polymers; D011956:Receptors, Cell Surface; C072032:thrombin receptor peptide (42-55); D014443:Tyrosine; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins