Interplay between the heterotrimeric G-protein subunits Gαq and Gαi2 sets the threshold for chemotaxis and TCR activation

Jacob Ngai, Marit Inngjerdingen, Torunn Berge, Kjetil Taskén
2009 BMC Immunology  
TCR 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 G αq and G αi2 have been implicated in CXCR4-signaling and we have recently also reported the possible involvement of G αq in TCR-dependent activation of Lck (Ngai et al., Eur. J. Immunol., 2008, 38: 32083218). Here we examined the
more » ... role of G αq in migration and TCR activation. Results: Pre-treatment of T cells with CXCL12 led to significantly reduced Lck Y394 phosphorylation upon TCR triggering indicating heterologous desensitization. We show that knockdown of G αq significantly enhanced basal migration in T cells and reduced CXCL12-induced SHP-1 phosphorylation whereas G αi2 knockdown inhibited CXCL12-induced migration. Conclusion: Our data suggest that G αi2 confers migration signals in the presence of CXCL12 whereas G αq exerts a tonic inhibition on both basal and stimulated migrational responses. This is compatible with the notion that the level of G αq activation contributes to determining the commitment of the T cell either to migration or activation through the TCR.
doi:10.1186/1471-2172-10-27 pmid:19426503 pmcid:PMC2694176 fatcat:32y6udr2zbal7bppyxumw4rvqy