Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases.
The high-affinity IgE receptor (Fc epsilon RI), which is expressed on the surface of mast cells and basophils, has a central role in immediate allergic responses. In the rat basophilic leukaemia cell line RBL-2H3, which is a model system for the analysis of Fc epsilon RI-mediated signal transduction, surface engagement of Fc epsilon RI induces histamine release and the tyrosine phosphorylation of several distinct proteins. Although the alpha, beta, and gamma subunits of Fc epsilon RI lack intrinsic tyrosine protein kinase (TPK) activity, a kinase that copurifies with Fc epsilon RI phosphorylates the beta and gamma subunits of the receptor on tyrosine residues. We report here that in RBL-2H3 cells, p56lyn and pp60c-src are activated after Fc epsilon RI crosslinking, and p56lyn coimmunoprecipitates with Fc epsilon RI. In the mouse mast-cell line PT-18, another cell type used to study FC epsilon RI-mediated signalling, tyrosine phosphorylation of proteins is also an immediate consequence of receptor crosslinking. Notably, the only detectable src protein-related TPK in PT-18 cells is p62c-yes, and it is this TPK that is activated on Fc epsilon RI engagement and coimmunoprecipitates with the receptor. Therefore, it seems that different src protein-related TPKs can associate with the same receptor and become activated after receptor engagement.
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical, Research Institute, Princeton, New Jersey 08543-4000.
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Bolen
D019297:2,4-Dinitrophenol; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D002460:Cell Line; D004140:Dinitrophenols / Q000276:immunology / Q000494:pharmacology; D004789:Enzyme Activation; D007073:Immunoglobulin E / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D019061:src-Family Kinases
D000944:Antigens, Differentiation, B-Lymphocyte; D004140:Dinitrophenols; D011961:Receptors, Fc; D017455:Receptors, IgE; D019000:Phosphotyrosine; D007073:Immunoglobulin E; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D019297:2,4-Dinitrophenol