Clustering of the platelet Fc gamma receptor induces noncovalent association with the tyrosine kinase p72syk.
The Fc receptor for IgG in platelets was identified as the integral membrane isoform encoded by the Fc gamma RIIA gene. Functional analysis of this molecule determined that activated Fc gamma RIIA is tyrosine phosphorylated and that activation induced the physical association with the protein tyrosine kinase p72syk. Other tyrosine-phosphorylated molecules also co-immunoadsorbed with the activated receptor. Tyrosine kinase activity co-immunoadsorbing with the platelet Fc gamma R was enhanced upon activation and specifically induced the phosphorylation, on tyrosine residues, of a physically associated 72-kDa protein. These data support a model of Fc gamma receptor-mediated platelet activation where signal is transduced through inducible association of the tyrosine kinase p72syk with the low affinity Fc gamma receptor. Thrombin, a potent platelet agonist, has been shown to up-regulate the activity of the tyrosine kinase p72syk in platelets. Consequently, our findings identify a second pathway by which p72syk is activated in platelets.
Chacko
G W
GW
Department of Internal Medicine, Ohio State University, Columbus 43210.
Duchemin
A M
AM
Coggeshall
K M
KM
Osborne
J M
JM
Brandt
J T
JT
Anderson
C L
CL
D015703:Antigens, CD; D001792:Blood Platelets / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011940:Receptor Aggregation; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase
D015703:Antigens, CD; D004792:Enzyme Precursors; C080568:Fc gamma receptor IIA; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase