The c-Abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19.
c-Abl is a nonreceptor tyrosine kinase that we have recently linked to growth factor receptor signaling. The c-Abl kinase is ubiquitously expressed and localizes to the cytoplasm, plasma membrane, cytoskeleton, and nucleus. Thus, c-Abl may regulate signaling processes in multiple subcellular compartments. Targeted deletion or mutation of c-Abl in mice results in a variety of phenotypes, including splenic and thymic atrophy and lymphopenia. Additionally, lymphocytes isolated from specific compartments of c-Abl mutant mice have reduced responses to a variety of stimuli and an increased susceptibility to apoptosis following growth factor deprivation. Despite these observations, little is known regarding the signaling mechanisms responsible for these phenotypes. We report here that splenic B cells from c-Abl-deficient mice are hyporesponsive to the proliferative effects of B cell Ag receptor (BCR) stimulation. The c-Abl kinase activity and protein levels are elevated in the cytosol following activation of the BCR in B cell lines. We show that c-Abl associates with and phosphorylates the BCR coreceptor CD19, and that c-Abl and CD19 colocalize in lipid membrane rafts. These data suggest a role for c-Abl in the regulation of B cell proliferation downstream of the BCR, possibly through interactions with CD19.
Zipfel
P A
PA
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Grove
M
M
Blackburn
K
K
Fujimoto
M
M
Tedder
T F
TF
Pendergast
A M
AM
D000818:Animals; D021461:Animals, Outbred Strains; D018941:Antigens, CD19 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D003902:Detergents; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016315:Proto-Oncogene Proteins c-abl / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism* / Q000502:physiology; D012995:Solubility; D013379:Substrate Specificity / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D018941:Antigens, CD19; D003902:Detergents; D011947:Receptors, Antigen, B-Cell; D016315:Proto-Oncogene Proteins c-abl