src-family tyrosine kinase p55fgr is expressed in murine splenic B cells and is activated in response to antigen receptor cross-linking.
Stimulation of the B cell Ag receptor (BCR) triggers a complex cascade of intracellular signals that lead to activation, proliferation, and differentiation. One of the earliest and most critical events following Ag receptor cross-linking is the activation of receptor-associated tyrosine kinases, which phosphorylate a variety of substrates involved in transducing signals generated through the receptor. Several tyrosine kinases have been shown to be associated with the BCR, including the src family members Lyn, Fyn, Blk, and Lck and the non-src kinase Syk. Here we describe another src family kinase expressed in B cells, p55fgr. Although previous studies have suggested that Fgr expression in the mouse is restricted to cells of the myeloid lineage, we demonstrate that highly purified murine splenic B cells express the kinase as well. We also show that Fgr, like other B cell kinases, is activated in response to cross-linking of the Ag receptor. Unlike these other kinases, however, Fgr does not appear to be physically associated with the receptor, and does not become activated until several minutes after stimulation. Moreover, we find that Fgr is associated with a distinct set of cellular proteins. On the basis of these studies, we hypothesize that Fgr may play a unique role in the BCR-associated signaling pathway.
Wechsler
R J
RJ
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104.
Monroe
J G
JG
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology*; D015153:Blotting, Western; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology; D019061:src-Family Kinases
D000936:Antigen-Antibody Complex; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; D011505:Protein-Tyrosine Kinases; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases