Multiple components of the B cell antigen receptor complex associate with the protein tyrosine phosphatase, CD45.
Signal transduction via the B cell antigen receptor complex is regulated by changes in tyrosine phosphorylation of several proteins. The equilibrium between tyrosine phosphorylation and dephosphorylation is regulated by the combined action of protein tyrosine kinase and protein tyrosine phosphatase enzymes. In particular, the protein tyrosine phosphatase, CD45, has been shown to play an essential role in signal transduction via the B cell antigen receptor. Therefore, experiments were performed to examine the intermolecular associations between CD45 and phosphotyrosine-containing proteins in the B cell to identify potential substrates for CD45. Based on coprecipitation experiments, CD45 was found to be physically associated with multiple components of the B cell antigen receptor complex including the MB-1/B29 heterodimer. Additionally, CD45 was selectively associated with the src family protein tyrosine kinase, lyn. Neither blk nor fyn were observed to interact with CD45 even though they have been implicated in antigen receptor signal transduction. This finding suggests that CD45 may preferentially regulate the phosphorylation of lyn and thus, its activity. In summary, these studies provide evidence to support the hypothesis that CD45 regulates antigen receptor-mediated signal transduction by controlling the tyrosine phosphorylation of multiple components of the antigen receptor complex.
Brown
V K
VK
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Ogle
E W
EW
Burkhardt
A L
AL
Rowley
R B
RB
Bolen
J B
JB
Justement
L B
LB
D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000378:metabolism*; D051925:CD79 Antigens; D007072:Immunoglobulin D / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009665:Noscapine / Q000031:analogs & derivatives / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D044005:Tetrahydroisoquinolines; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D019061:src-Family Kinases
D015703:Antigens, CD; D051925:CD79 Antigens; C497884:Cd79b protein, mouse; D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D044005:Tetrahydroisoquinolines; D019000:Phosphotyrosine; D014443:Tyrosine; C029088:l-alpha-methyl-8-methoxy-6,7-dihydroxy-1-(6,7-dimethoxy-3-phthalidyl)-1,2,3,4-tetrahydroisoquinoline; D009665:Noscapine; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens