Cytohesin binder and regulator augments T cell receptor-induced nuclear factor of activated T Cells.AP-1 activation through regulation of the JNK pathway.
Cytohesin binder and regulator (Cybr; also known as CYTIP, CASP, and PSCDBP) is a cytokine-induced gene preferentially expressed in hematopoietic tissues and in T helper 1 cells. Cybr protein associates with members of the cytohesin family, which are known ADP-ribosylation factors-GDP/GTP exchange factors, and its functions appear to regulate lymphocyte adhesion and cell-cell contact. Here we show that Cybr mRNA and protein levels are increased upon T cell receptor engagement. Cybr expression then influences T cell receptor-dependent signaling events, such as nuclear factor of activated T cells and AP-1 transcriptional activity. In addition, expression of Cybr results in increased T cell receptor-mediated activation of the Rho/Rac exchange factor Vav and of the JNK-p38 MAPK signaling pathway. The effects of Cybr on nuclear factor of activated T cells and AP-1 are dependent on MAPK activation, and enhanced activation of this cascade results in cooperation between the two transcription factors in the regulation of gene expression. These findings provide the first evidence that the adaptor protein Cybr not only regulates lymphocyte adhesion and cell-cell interaction but also contributes to the regulation of the signaling cascade and of the genetic program downstream of the T cell receptor.
Chen
Qian
Q
Division of Infection and Immunity, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast BT9 7BL, UK.
Coffey
Alan
A
Bourgoin
Sylvain G
SG
Gadina
Massimo
M
D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic
C084539:CYTIP protein, human; D017931:DNA Primers; D018076:DNA, Complementary; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D048670:MAP Kinase Kinase 4