title: The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen.
abstract: Activation of mouse platelets by collagen is associated with tyrosine phosphorylation of multiple proteins including the Fc receptor gamma-chain, the tyrosine kinase Syk and phospholipase Cgamma2, suggesting that collagen signals in a manner similar to that of immune receptors. This hypothesis has been tested using platelets from mice lacking the Fc receptor gamma-chain or Syk. Tyrosine phosphorylation of Syk and phospholipase Cgamma2 by collagen stimulation is absent in mice lacking the Fc receptor gamma-chain. Tyrosine phosphorylation of phospholipase Cgamma2 by collagen stimulation is also absent in mice platelets which lack Syk, although phosphorylation of the Fc receptor gamma-chain is maintained. In contrast, tyrosine phosphorylation of platelet proteins by the G protein-coupled receptor agonist thrombin is maintained in mouse platelets deficient in Fc receptor gamma-chain or Syk. The absence of Fc receptor gamma-chain or Syk is accompanied by a loss of secretion and aggregation responses in collagen- but not thrombin-stimulated platelets. These observations provide the first direct evidence of an essential role for the immunoreceptor tyrosine-based activation motif (ITAM) in signalling by a non-immune receptor stimulus.
authors.affiliation: Department of Pharmacology, University of Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Poole
authors.forename: J M
authors.initials: JM
authors.lastname: Gibbins
authors.forename: M
authors.initials: M
authors.lastname: Turner
authors.forename: M J
authors.initials: MJ
authors.lastname: van Vugt
authors.forename: J G
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: V L
authors.initials: VL
authors.lastname: Tybulewicz
authors.forename: S P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001760:Bleeding Time; D003094:Collagen / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D051966:Phospholipase C gamma; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation; D010976:Platelet Count; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D013917:Thrombin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D017452:Receptors, IgG; D016718:Arachidonic Acid; D012701:Serotonin; D014443:Tyrosine; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D013917:Thrombin