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SIGNALING THROUGH CD19 ACTIVATES VAV MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAY AND INDUCES FORMATION OF A CD19/VAV/PHOSPHATIDYLINOSITOL 3-KINASE COMPLEX IN HUMAN B-CELL PRECURSORS

SIGNALING THROUGH CD19 ACTIVATES VAV MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAY AND INDUCES FORMATION OF A CD19/VAV/PHOSPHATIDYLINOSITOL 3-KINASE COMPLEX IN HUMAN B-CELL PRECURSORS JOURNAL OF BIOLOGICAL CHEMISTRY Weng, W. K., Jarvis, L., LeBien, T. W. 1994; 269 (51): 32514-32521

Abstract

The B cell-specific cell surface molecule CD19 plays a role in regulating immunoglobulin (Ig) receptor signaling, and cross-linking CD19 activates several signaling molecules in mature human B cells. In surface Ig-negative B cell precursors, a protein tyrosine kinase (PTK)-dependent homotypic aggregation response can be triggered by cross-linking CD19. In the current study, we examined the outcome of PTK-mediated signal transduction following CD19 cross-linking on surface Ig negative and surface Ig positive B cell lines, as well as freshly isolated surface Ig-negative B cell precursors. PTK activation resulted in the tyrosine phosphorylation of multiple protein substrates and peaked at 0.5-1 min following CD19 cross-linking in all B-lineage cells examined. One of the tyrosine-phosphorylated substrates was identified as the hematopoietic-specific protein Vav, a guanine nucleotide exchange factor that activates the Ras pathway. Evidence consistent with Ras pathway activation was also demonstrated by MEK activation and subsequent phosphorylation of a MAP kinase fusion protein. CD19 cross-linking, sequential immunoprecipitation, and Western blotting revealed that: (a) Vav becomes associated with CD19, (b) phosphatidylinositol 3-kinase (PI 3-kinase) becomes associated with CD19, and (c) PI 3-kinase becomes associated with Vav. No such physical interaction occurred following control IgG1 cross-linking or cross-linking of class I major histocompatability complex cell surface molecules. Coupled with a previous report (Tuveson, D.A., Carter, R.H., Soltoff, S.P., and Fearon, D.T. (1993) Science 260, 986-988), our data support a model in which CD19 cross-linking induces the formation of a signaling complex that leads to the activation of two pathways involving Ras and PI 3-kinase.

View details for Web of Science ID A1994PX30400074

View details for PubMedID 7528218