Activation of lyn, blk, and btk but not syk in CD72-stimulated B lymphocytes.
CD72 is a B cell-specific glycoprotein that has been shown to be important for activation of mature B cells. Previously we showed that some of the early signaling events, such as calcium mobilization and phospholipase-gamma activation, were similar in B cell Ag receptor (BCR)- and CD72-stimulated B cells and that BCR- but not CD72-mediated early signaling events were blocked by protein kinase A activation. The present report shows that CD72 ligation induces a variety of tyrosine-phosphorylated proteins, most of which were of the same molecular mass as those seen in anti-IgM-treated B cells, except for a 72-kDa protein. Further analysis showed that the tyrosine kinases lyn and blk were activated in CD72-ligated B cells. Interestingly, the non-src kinase syk was not activated in CD72-stimulated cells whereas the tec family kinase btk was activated in both CD72- and BCR-stimulated B cells. Furthermore, B cells from xid mice were unresponsive to CD72-induced proliferation, indicating an essential role for btk in CD72-induced signaling events. Surprisingly, tyrosine phosphorylation of phospholipase C-gamma2 was normal in CD72-stimulated cells in spite of a lack of activation of syk. Furthermore, B cell proliferation through CD72 was blocked by the immunosuppressive agents cyclosporin A and FK506, indicating the important role for Ca2+-regulated activation events similar to BCR-stimulated cells. We propose that btk can substitute for syk in inducing phospholipase C-gamma2 tyrosine phosphorylation and initiating calcium mobilization in CD72-stimulated B lymphocytes.
Venkataraman
C
C
Department of Microbiology and Immunology, Sanders-Brown Center on Aging, University of Kentucky, Lexington 40536, USA.
Muthusamy
N
N
Muthukkumar
S
S
Bondada
S
S
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism*; D005260:Female; D007108:Immune Tolerance / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013379:Substrate Specificity / Q000276:immunology; D000072377:Syk Kinase; D016559:Tacrolimus / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014960:X Chromosome / Q000276:immunology; D019061:src-Family Kinases / Q000378:metabolism*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C064228:CD72 protein, human; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D014443:Tyrosine; D016572:Cyclosporine; C082599:protein-tyrosine kinase p55(blk); D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D010738:Type C Phospholipases; D016559:Tacrolimus