Role of the Src family kinase Lyn in TxA2 production, adenosine diphosphate secretion, Akt phosphorylation, and irreversible aggregation in platelets stimulated with gamma-thrombin.
Members 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 gamma-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 gamma-thrombin concentrations that cause secretion-dependent irreversible aggregation. Phosphorylation of Akt, a downstream effector of phosphatidylinositol 3-kinase, also requires a higher concentration of gamma-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.
Cho
Moon J
MJ
Department of Microbiology and Molecular Cell Sciences, University of Memphis, Memphis, TN 38152, USA.
Pestina
Tamara I
TI
Steward
Shirley A
SA
Lowell
Clifford A
CA
Jackson
Carl W
CW
Gartner
T Kent
TK
D000244:Adenosine Diphosphate / Q000097:blood*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000097:blood*; D051057:Proto-Oncogene Proteins c-akt; D013917:Thrombin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000097:blood*; D019061:src-Family Kinases / Q000097:blood / Q000172:deficiency / Q000235:genetics*
D000244:Adenosine Diphosphate; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D013917:Thrombin; D013928:Thromboxane A2; D019061:src-Family Kinases; C060902:lyn protein-tyrosine kinase