Regulators of G protein signaling exhibit distinct patterns of gene expression and target G protein specificity in human lymphocytes

The newly recognized regulators of G protein signaling (RGS) attenuate hete rotrimeric G protein signaling pathways. We have cloned an IL-2-induced gen e from human T cells, cytokine-responsive gene 1, which encodes a member of the RGS family, RGS16. The RGS16 protein binds G(i alpha) and G(q alpha) p roteins present in T cells, and inhibits G(i)- and G(q)-mediated signaling pathways. By comparison, the mitogen-induced RGS2 inhibits G(q) but not G(i ) signaling. Moreover, the two RGS genes exhibit marked differences in expr ession patterns. The IL-2-induced expression of the RGS16 gene in T cells i s suppressed by elevated cAMP, whereas the RGS2 gene shows a reciprocal pat tern of regulation by these stimuli. Because the mitogen and cytokine recep tors that trigger expression of RGS2 and RGS16 in T cells do not activate h eterotrimeric G proteins, these RGS proteins and the G proteins that they r egulate may play a heretofore unrecognized role in T cell functional respon ses to Ag and cytokine activation.