Activation of three classes of nonreceptor tyrosine kinases following Fc gamma receptor crosslinking in human monocytes.
Fc gamma receptors on monocytes/macrophages play an important role in both host defense and autoimmune disorders. Fc gamma receptor signaling can lead to such downstream events as phagocytosis and the release of intracellular cytokines and reactive oxygen species. Freshly isolated human monocytes express two major classes of Fc gamma receptor proteins, Fc gamma RI (CD64) and Fc gamma RII (CD32). Crosslinking of Fc gamma RI and Fc gamma RII gives rise to rapid and transient phosphorylation of multiple monocyte intracellular proteins including proteins of 40, 68-72, 75-85, 95, and 115-165 kDa. A 72-kDa protein was earlier identified as the tyrosine kinase Syk. Here we identify one of the proteins in the 115- to 165-kDa cluster as FAK, a protein tyrosine kinase localized to focal adhesions. A 68-kDa phosphoprotein was identified as paxillin, a cytoskeleton associated substrate for tyrosine kinases, and a 95-kDa protein was found to be the proto-oncogene product Vav. The Src family protein tyrosine kinase Fgr (p58) also displayed enhanced tyrosine phosphorylation after Fc gamma RI and Fc gamma RII crosslinking. Although Fc gamma RIIA utilizes tyrosines within its own cytoplasmic domain for signaling while Fc gamma RI utilizes the cytoplasmic tyrosines of its associated gamma subunit, our results indicate sharing of several proteins for signaling in monocytes by these Fc receptors. These molecules include three distinct classes of tyrosine kinases, Syk, FAK, and Fgr, and the functionally diverse proteins Vav and paxillin.
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Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA.
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D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D009000:Monocytes / Q000201:enzymology* / Q000648:ultrastructure*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000097:blood* / Q000145:classification* / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D017452:Receptors, IgG / Q000097:blood* / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C000715470:MAS1 protein, human; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human