[The role of vav protein in TCR-mediated signaling with MHC/peptide complexes leading to positive or negative selection of thymocytes].
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.
Matuszyk
J
J
Laboratorium Immunologii Komórkowej, Instytutu Immunologii i Terapii Doświadczalnej PAN, Wrocławiu.
Kałas
W
W
Kozicki
R
R
Strzadała
L
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008285:Major Histocompatibility Complex / Q000502:physiology; D015513:Oncogene Proteins / Q000378:metabolism*; D010766:Phosphorylation; D051567:Proto-Oncogene Proteins c-vav; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013950:Thymus Gland / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; D015513:Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C496618:VAV1 protein, human