J Matuszyk 1 , W Kałas , R Kozicki , L Strzadała
1. Laboratorium Immunologii Komórkowej, Instytutu Immunologii i Terapii DoświadczalnejPAN, Wrocławiu.
Published:
GICID: 01.3001.0000.3235
Available language versions: en pl
Issue: Postepy Hig Med Dosw 1999; 53 (4)
Abstract
On the basis of recent reports we discuss the role of Vav in TCR-dependent signaling pathways. The Vav protein is GDP/GTP exchange factor for Rac, which initiates transduction of signals in JNK pathway. Upon stimulation of TCR by antigenic peptides, Vav associates with Zap-70 in TCR/CD3 signaling complex and becomes phosphorylated on Tyr-174 by tyrosine kinase Lck. The function of Vav is modulated by substrates and products of PI3-kinase activated by interaction of CD28 on thymocytes with B7 on antigen presenting cells. The PI3-kinase substrates inhibit activation of Vav, while the products enhance phosphorylation and activation of Vav by Lck. It seems that Vav functions in key point of TCR-mediated signaling pathway, which is regulated by costimulatory molecule (CD28) necessary for negative selection. The Vav-mediated integration of signals results in positive or negative selection of thymocytes.