title: Platelet adhesion and signaling induced by the octapeptide primary binding sequence (KOGEOGPK) from type III collagen.
abstract: Platelet adhesion to vascular collagens is an essential step in the initiation of hemostasis and thrombosis. Several platelet receptors interact with type I and type III collagens, including GP Ia/IIa and GP VI. We recently described a new platelet receptor (TIIICBP) specific for a type III collagen-related primary binding sequence, the KOGEOGPK octapeptide. Here, we characterize platelet adhesion to the immobilized octapeptide and demonstrate that this adhesion 1) is Ca2+ and Mg2+ independent, suggesting a noninvolvement of GP Ia/IIa; 2) is not inhibited by an antibody against GP VI; and 3) triggers platelet protein tyrosine phosphorylation. Whereas TXA2 has minimal effects, released ADP via only P2Y12 potentiates platelet adhesion to the octapeptide. Octapeptide-induced platelet adhesion triggers platelet signaling through tyrosine phosphorylation of the 68 kDa subunit of TIIICBP, Syk, PLCgamma2, and FAK. Tyrosine phosphorylation of the FcR gamma-chain and LAT is also observed but to a lesser extent than with type III collagen, suggesting the requirement of GP VI for full tyrosine phosphorylation of FcR gamma-chain and LAT. The present study provides evidence for a critical role for the type III collagen-related KOGEOGPK octapeptide in mediating platelet adhesion and signaling, and consequently in platelet-collagen interactions.-
authors.affiliation: U553 INSERM: Hémostase, Endothélium et Angiogénèse, Institut d'Hématologie, Université Paris VII-Denis Diderot, IFR Saint-Louis, Hôpital Saint-Louis, Paris Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Maurice
authors.forename: Chantal
authors.initials: C
authors.lastname: Legrand
authors.forename: Françoise
authors.initials: F
authors.lastname: Fauvel-Lafeve
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002413:Cations, Divalent / Q000494:pharmacology; D002417:Cattle; D024061:Collagen Type III / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003435:Crotalid Venoms / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051966:Phospholipase C gamma; D010766:Phosphorylation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D038981:Receptors, Collagen / Q000737:chemistry / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000072377:Syk Kinase; D013928:Thromboxane A2 / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D024061:Collagen Type III; D003435:Crotalid Venoms; D016861:Cyclooxygenase Inhibitors; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D021122:Protein Subunits; D058919:Purinergic P2 Receptor Antagonists; D038981:Receptors, Collagen; D018048:Receptors, Purinergic P2; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase; D010738:Type C Phospholipases; D051966:Phospholipase C gamma