Association of non-receptor protein tyrosine kinases with the Fc gamma RI/gamma-chain complex in monocytic cells.
To characterize the functional macromolecular complex of the high affinity receptor for IgG (Fc gamma RI), we have undertaken the identification of the molecules associated with the ligand binding unit and its associated subunit, gamma-chain, in a monocyte cell line, U937. Comparison of the pattern of tyrosine-phosphorylated proteins that coprecipitate with anti-Fc gamma RI or anti-gamma-chain Abs after Fc gamma RI clustering suggests that, like other receptor systems, the different units of the receptor associate or recruit different elements of the signaling pathway. Syk associates preferentially with the gamma-chain subunit and not with Fc gamma RI itself. This association is dependent on receptor clustering and correlates with gamma-chain phosphorylation. The Src kinase Lyn is also part of the receptor complex. Lyn associates with both units of the receptor, and this association is independent of receptor engagement; however, the level of tyrosine phosphorylation of the kinase increases after Fc gamma RI clustering. Association of a 35-kDa phosphoprotein with the binding unit was also observed after receptor clustering. We further found that after Fc gamma RI clustering, tyrosine-phosphorylated Syk associates with Lyn. These data suggest that several levels of interaction occur between these molecules or that different pools of tyrosine kinases become activated after Fc gamma RI clustering.
Duchemin
A M
AM
Department of Internal Medicine, Ohio State University College of Medicine, Columbus, OH 43210, USA.
Anderson
C L
CL
D000936:Antigen-Antibody Complex / Q000276:immunology*; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000276:immunology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D016403:Lymphoma, Large B-Cell, Diffuse; D009000:Monocytes / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism
D000936:Antigen-Antibody Complex; D004792:Enzyme Precursors; D007142:Immunoglobulin gamma-Chains; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases