Regulator of G protein signaling 1 (RGS1) markedly impairs Giα signaling responses of B lymphocytes

Regulator of G protein signaling (RGS) proteins modulate signaling through pathways that use heterotrimeric G proteins as transducing elements. RGS1 is expressed at high levels in certain B cell lines and can be induced in normal B cells by treatment with TNF-alpha. To determine the signaling pathways that RGS1 may regulate, we examined the specificity of RGS1 for various G, subunits and assessed its effect on chemokine signaling. G protein binding and GTPase assays revealed that RGS1 is a G,, and G(q alpha) GTPase-activating protein and a potential G(12 alpha) effector antagonist, Functional studies demonstrated that RGS1 impairs platelet activating factor-mediated increases in intracellular Ca+2, stromal-derived factor-1-induced cell migration, and the induction of downstream signaling by a constitutively active form of G(12 alpha). Furthermore, germinial center B lymphocytes, which are refractory to stromal-derived factor-1-triggered migration, express high levels of RGS1, These results indicate that RGS proteins can profoundly effect the directed migration of lymphoid cells.