Vav1 transduces T cell receptor signals to the activation of phospholipase C-gamma 1 via phosphoinositide 3-kinase-dependent and -independent pathways
Author(s)
Type
Journal Article
Abstract
Vav1 is a signal transducing protein required for T cell receptor (TCR) signals that drive positive and negative selection in the thymus. Furthermore, Vav1-deficient thymocytes show greatly reduced TCR-induced intracellular calcium flux. Using a novel genetic system which allows the study of signaling in highly enriched populations of CD4+CD8+ double positive thymocytes, we have studied the mechanism by which Vav1 regulates TCR-induced calcium flux. We show that in Vav1-deficient double positive thymocytes, phosphorylation, and activation of phospholipase C-γ1 (PLCγ1) is defective. Furthermore, we demonstrate that Vav1 regulates PLCγ1 phosphorylation by at least two distinct pathways. First, in the absence of Vav1 the Tec-family kinases Itk and Tec are no longer activated, most likely as a result of a defect in phosphoinositide 3-kinase (PI3K) activation. Second, Vav1-deficient thymocytes show defective assembly of a signaling complex containing PLCγ1 and the adaptor molecule Src homology 2 domain–containing leukocyte phosphoprotein 76. We show that this latter function is independent of PI3K.
Date Issued
2002-04-29
Date Acceptance
2002-03-19
Citation
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (9), pp.1103-1114
ISSN
0022-1007
Publisher
Rockefeller University Press
Start Page
1103
End Page
1114
Journal / Book Title
JOURNAL OF EXPERIMENTAL MEDICINE
Volume
195
Issue
9
Copyright Statement
© 2002 Rockefeller University Press
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000176110700003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
thymus
Itk
Tec
Rac1
SLP-76
INDUCED TYROSINE PHOSPHORYLATION
PLECKSTRIN HOMOLOGY DOMAIN
EXCHANGE FACTOR VAV
PROTOONCOGENE PRODUCT
RHO-FAMILY
PHOSPHATIDYLINOSITOL 3-KINASE
B-CELL
ADAPTER PROTEIN
TEC KINASES
C-GAMMA
Publication Status
Published