Involvement of p72syk, a protein-tyrosine kinase, in Fc gamma receptor signaling.
Previous studies have demonstrated that multichain immune recognition receptors, such as the T-cell receptor, signal their occupancy by inducing tyrosine phosphorylation of cellular protein substrates. Type I and II receptors for the Fc portion of IgG are single-chain immune recognition receptors having external, transmembrane, and cytoplasmic domains. In the present study, we have investigated the possibility that, upon engagement, Fc gamma receptors induce protein-tyrosine phosphorylation. Our findings reveal increased phosphorylation of a number of proteins on tyrosine residues after cross-linking of either high (Fc gamma RI) or low (Fc gamma RII) affinity receptors expressed on HL60 cells. Engagement of Fc gamma RII induced rapid tyrosine phosphorylation that decayed to basal levels by 40 min. In contrast, phosphorylation induced by Fc gamma RI cross-linking was more delayed, peaking at 5-10 min, and returning to basal levels by 60 min. Kinase assays of cellular proteins immunoprecipitated from lysates of activated cells by antibody to phosphotyrosine revealed phosphorylation of a 72-kDa molecule that was not present in lysates of resting cells. This phosphoprotein was identified as p72syk by immunoprecipitation with antibodies directed against two different regions of the syk gene product. Immunoprecipitation with antibodies against p72syk followed by immunoblotting with anti-phosphotyrosine antibodies revealed an activation-dependent tyrosine phosphorylation of p72syk. Thus, our present findings demonstrate induction of protein-tyrosine phosphorylation following engagement of monomeric immune recognition receptors and identify p72syk as a tyrosine kinase substrate involved in signaling by Fc gamma RI and Fc gamma RII.
Agarwal
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A
Laboratory of Cellular Development and Oncology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Salem
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P
Robbins
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KC
D002460:Cell Line; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism
D003432:Cross-Linking Reagents; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase