Tyrosine kinase and CD45 tyrosine phosphatase activity mediate p21(ras) activation in B cells stimulated through the antigen receptor

K. Kawauchi, A. H. Lazarus, M. J. Rapoport, A. Harwood, J. C. Cambier, T. L. Delovitch

Research output: Contribution to journalArticlepeer-review

Abstract

Cross-linking of the Ag receptor (AgR) induces intracellular signaling events in B cells, such as p21(ras) activation, that lead to their proliferation and differentiation. This event is accompanied by the tyrosine phosphorylation of the p21(ras)-associated GTPase-activating protein p120 ras. GAP, raising the possibility that AgR-stimulated p21(ras) activity is regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases) in B cells. To test this possibility, we examined the effects of PTK and PTPase inhibitors on protein tyrosine phosphorylation and p21(ras) activation induced by AgR cross-linking in TNP-specific TA3 7.9 murine B lymphoma cells. Although AgR-induced protein tyrosine phosphorylation was inhibited by the PTK inhibitors genistein and herbimycin A, it was enhanced by exposure to the PTPase inhibitor phenylarsine oxide (PAO). Cross-linking of the AgR by Ag or F(ab')2 anti-IgM induced a rapid (within 5 min) two- to threefold increase in p21(ras) activation in 7.9 B cells. Interestingly, a second peak of p21(ras) activation was evident at approximately 40 min after stimulation. Genistein and herbimycin A and PAO each blocked AgR-stimulated p21(ras) activation. Similarly, Ag-induced p21(ras) activation was inhibited by pretreatment of 7.9 B cells with an anti-CD45 mAb (detects the 220-kDa B cell isoform of CD45). Moreover, p21(ras) activation was induced by Ag and F(ab')2 anti-IgM in CD45+ but not CD45- J558Lμm3 B cells. These data indicate that p21(ras) activation induced by AgR cross-linking in B cells is regulated by both PTK and CD45 PTPase activities.

Original languageEnglish
Pages (from-to)3306-3316
Number of pages11
JournalJournal of Immunology
Volume152
Issue number7
StatePublished - 1994
Externally publishedYes

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