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Tyrosine kinase and CD45 tyrosine phosphatase activity mediate p21ras activation in B cells stimulated through the antigen receptor. 1994

K Kawauchi, and A H Lazarus, and M J Rapoport, and A Harwood, and J C Cambier, and T L Delovitch
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.

Cross-linking of the Ag receptor (AgR) induces intracellular signaling events in B cells, such as p21ras activation, that lead to their proliferation and differentiation. This event is accompanied by the tyrosine phosphorylation of the p21ras-associated GTPase-activating protein p120 ras.GAP, raising the possibility that AgR-stimulated p21ras 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 p21ras 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 p21ras activation in 7.9 B cells. Interestingly, a second peak of p21ras activation was evident at approximately 40 min after stimulation. Genistein and herbimycin A and PAO each blocked AgR-stimulated p21ras activation. Similarly, Ag-induced p21ras 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, p21ras activation was induced by Ag and F(ab')2 anti-IgM in CD45+ but not CD45- J558L microns 3 B cells. These data indicate that p21ras activation induced by AgR cross-linking in B cells is regulated by both PTK and CD45 PTPase activities.

UI MeSH Term Description Entries
D010047 Ovalbumin An albumin obtained from the white of eggs. It is a member of the serpin superfamily. Serpin B14
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011947 Receptors, Antigen, B-Cell IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment. Antigen Receptors, B-Cell,B-Cell Antigen Receptor,B-Cell Antigen Receptors,Surface Immunoglobulin,Immunoglobulins, Membrane-Bound,Immunoglobulins, Surface,Membrane Bound Immunoglobulin,Membrane-Bound Immunoglobulins,Receptors, Antigen, B Cell,Surface Immunoglobulins,Antigen Receptor, B-Cell,Antigen Receptors, B Cell,B Cell Antigen Receptor,B Cell Antigen Receptors,Bound Immunoglobulin, Membrane,Immunoglobulin, Membrane Bound,Immunoglobulin, Surface,Immunoglobulins, Membrane Bound,Membrane Bound Immunoglobulins,Receptor, B-Cell Antigen,Receptors, B-Cell Antigen
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000941 Antigens Substances that are recognized by the immune system and induce an immune reaction. Antigen
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D014443 Tyrosine A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin. L-Tyrosine,Tyrosine, L-isomer,para-Tyrosine,L Tyrosine,Tyrosine, L isomer,para Tyrosine
D016283 Proto-Oncogene Proteins p21(ras) Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47. Proto-Oncogene Proteins c-ras,c-Ha-ras p21,c-Ki-ras p21,p21(N-ras),p21(c-Ha-ras),p21(c-Ki-ras),p21(c-ras),p21(ras),ras Proto-Oncogene Protein p21,Proto-Oncogene Protein p21(c-Ha-ras),Proto-Oncogene Protein p21(c-Ki-ras),Proto-Oncogene Protein p21(c-N-ras),Proto-Oncogene Protein p21(ras),Proto-Oncogene Protein ras,c-ras Proteins,p21 c-H-ras,p21 c-Ha-ras,p21 c-K-ras,p21 c-Ki-ras,p21 c-ras,ras Proto-Oncogene Product p21,Proteins c-ras, Proto-Oncogene,Proto Oncogene Protein ras,Proto Oncogene Proteins c ras,c Ha ras p21,c Ki ras p21,c ras Proteins,c-H-ras, p21,c-Ha-ras, p21,c-K-ras, p21,c-Ki-ras, p21,c-ras, Proto-Oncogene Proteins,c-ras, p21,p21 c H ras,p21 c Ha ras,p21 c K ras,p21 c Ki ras,p21 c ras,p21, c-Ha-ras,p21, c-Ki-ras,ras Proto Oncogene Product p21,ras Proto Oncogene Protein p21,ras, Proto-Oncogene Protein

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