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PMID: 11805146 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation.

The Journal of experimental medicine ·Vol. 195 ·No. 2 ·2002-01-21 ·Pages 189-200

Inabe K, Ishiai M, Scharenberg AM, Freshney N, Downward J, Kurosaki T

Abstract

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.

MeSH Terms
Animals Calcium/immunology Cell Cycle Proteins Cell Line Chickens Guanine Nucleotide Exchange Factors Humans Phosphatidylinositol 3-Kinases/immunology Proto-Oncogene Proteins/genetics,immunology Proto-Oncogene Proteins c-vav Receptors, Antigen, B-Cell/genetics,immunology Signal Transduction/genetics,immunology rac1 GTP-Binding Protein/genetics,immunology
Chemicals
Cell Cycle Proteins Guanine Nucleotide Exchange Factors Proto-Oncogene Proteins Proto-Oncogene Proteins c-vav Receptors, Antigen, B-Cell VAV3 protein, human Phosphatidylinositol 3-Kinases rac1 GTP-Binding Protein Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Inabe Kazunori
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan.
Ishiai Masamichi
Scharenberg Andrew M
Freshney Norman
Downward Julian
Kurosaki Tomohiro
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20011571
Published
2002-01-21
Pages
189-200
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193613
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20011571 PMC Full Text View journal details
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