Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation.
To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here we report that Vav3 influences phosphoinositide 3-kinase (PI3K) function through Rac1 in that phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation was attenuated by loss of Vav3 or by expression of a dominant negative form of Rac1. The functional interaction between PI3K and Rac1 was also demonstrated by increased PI3K activity in the presence of GTP- bound Rac1. In addition, we show that defects of calcium mobilization and c-Jun NH2-terminal kinase ( JNK) activation in Vav3-deficient cells are relieved by deletion of a PIP3 hydrolyzing enzyme, SH2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP). Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux.[1]References
- Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation. Inabe, K., Ishiai, M., Scharenberg, A.M., Freshney, N., Downward, J., Kurosaki, T. J. Exp. Med. (2002) [Pubmed]
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