[The role of p21ras oncoprotein in signal transduction mediated through B cell antigen receptor (BCR)].
Ligation of B cell antigen receptor (BCR) with antigen or anti IgM leads to enter cells into the proliferation and differentiation to produce specific Ig. Protein tyrosine kinase (PTK) and CD 45 protein tyrosine phosphatase (PTP) both are involved in the early phase of BCR-mediated B cell signaling. We have investigated the role of p 21ras(ras) in B cell signal transduction using TNP-specific TA3 7.9 murine B cells. B cell stimulation with either TNP6-OVA(Ag) or anti-IgM resulted in rapid accumulation of GTP-bound(active) ras as well as induction of a number of tyrosine phosphorylated substrates. The accumulation of GTP-bound ras was blocked by the treatment with either PTK inhibitors(genistein) or PTP inhibitors(PAO), suggesting that BCR-mediated ras activation is regulated by both PTK and PTP including CD 45. As phosphorylation on tyrosine residues of Lyn, Fyn, and Blk protein tyrosine kinases occurred upon BCR stimulation, these PTKs may be candidates being involved in an induction of not only tyrosine phosphorylation of substrates but also p 21ras activation. Furthermore we found that rasGAP activity is suppressed following Ag stimulation, accompanied by the phosphorylation on tyrosine of rasGAP and its associated protein p 62. These data indicate that protein tyrosine kinases may alter rasGAP activity to induce p 21ras activation in B cells.
Kawauchi
K
K
Tokyo Women's Medical College Daini Hospital, Department of Medicine II, Japan.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D017493:Leukocyte Common Antigens; D051379:Mice; D008807:Mice, Inbred BALB C; D015689:Oncogene Protein p21(ras) / Q000378:metabolism / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction
D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D015689:Oncogene Protein p21(ras)