Interplay between the heterotrimeric G-protein subunits Gαq and Gαi2 sets the threshold for chemotaxis and TCR activation
Copyright policy )Interplay between the heterotrimeric G-protein subunits Gαq and Gαi2 sets the threshold for chemotaxis and TCR activation
AbstractBackgroundTCR and CXCR4-mediated signaling appears to be reciprocally regulated pathways. TCR activation dampens the chemotactic response towards the CXCR4 ligand CXCL12, while T cells exposed to CXCL12 are less prone to subsequent TCR-activation. The heterotrimeric G proteins Gαqand Gαi2have been implicated in CXCR4-signaling and we have recently also reported the possible involvement of Gαqin TCR-dependent activation of Lck (Ngai et al., Eur. J. Immunol., 2008, 38: 32083218). Here we examined the role of Gαqin migration and TCR activation.ResultsPre-treatment of T cells with CXCL12 led to significantly reduced Lck Y394 phosphorylation upon TCR triggering indicating heterologous desensitization. We show that knockdown of Gαqsignificantly enhanced basal migration in T cells and reduced CXCL12-induced SHP-1 phosphorylation whereas Gαi2knockdown inhibited CXCL12-induced migration.ConclusionOur data suggest that Gαi2confers migration signals in the presence of CXCL12 whereas Gαqexerts a tonic inhibition on both basal and stimulated migrational responses. This is compatible with the notion that the level of Gαqactivation contributes to determining the commitment of the T cell either to migration or activation through the TCR.
- University of Oslo Norway
Feedback, Physiological, 570, Receptors, CXCR4, Chemotaxis, Protein Tyrosine Phosphatase, Non-Receptor Type 6, T-Lymphocytes, Immunology, Receptors, Antigen, T-Cell, 610, RC581-607, Lymphocyte Activation, Chemokine CXCL12, Jurkat Cells, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Research article, GTP-Binding Protein alpha Subunits, Gq-G11, Humans, Immunologic diseases. Allergy, GTP-Binding Protein alpha Subunit, Gi2, RNA, Small Interfering, Signal Transduction
Feedback, Physiological, 570, Receptors, CXCR4, Chemotaxis, Protein Tyrosine Phosphatase, Non-Receptor Type 6, T-Lymphocytes, Immunology, Receptors, Antigen, T-Cell, 610, RC581-607, Lymphocyte Activation, Chemokine CXCL12, Jurkat Cells, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Research article, GTP-Binding Protein alpha Subunits, Gq-G11, Humans, Immunologic diseases. Allergy, GTP-Binding Protein alpha Subunit, Gi2, RNA, Small Interfering, Signal Transduction
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