Role of the Src family kinase Lyn in TxA2 production, adenosine diphosphate secretion, Akt phosphorylation, and irreversible aggregation in platelets stimulated with γ-thrombin
2002; Elsevier BV; Volume: 99; Issue: 7 Linguagem: Inglês
10.1182/blood.v99.7.2442
ISSN1528-0020
AutoresMoon J. Cho, Tamara I. Pestina, Shirley A. Steward, Clifford A. Lowell, Carl W. Jackson, T. Kent Gartner,
Tópico(s)Coagulation, Bradykinin, Polyphosphates, and Angioedema
ResumoMembers of the Src family of kinases are abundant in platelets. Although their localization is known, their role(s) in platelet function are not well understood. Lyn is a Src-family kinase that participates in signal transduction pathways elicited by collagen-related peptide; it has also been implicated through biochemical studies in the regulation of von Willebrand factor signaling. Here, we provide evidence that Lyn plays a role in γ-thrombin activation of platelets. Unlike the wild-type platelets, platelets from Lyn-deficient mice do not undergo irreversible aggregation, produce thromboxane A2, or secrete adenosine diphosphate in response to submaximal γ-thrombin concentrations that cause secretion-dependent irreversible aggregation. Phosphorylation of Akt, a downstream effector of phosphatidylinositol 3-kinase, also requires a higher concentration of γ-thrombin in Lyn-deficient platelets than in wild-type platelets. These findings demonstrate that Lyn signaling is required for thrombin induction of secretion-dependent platelet aggregation. Specifically, Lyn is required under these conditions to enable thrombin-induced TxA2 production and adenosine diphosphate secretion, necessary steps in secretion-dependent platelet aggregation.
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