Anti-RGS16 monoclonal antibody, clone 5D0

The newly recognized regulators of G protein signaling (RGS) attenuate heterotrimeric G protein signaling pathways. We have cloned an IL-2-induced gene 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) proteins 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 expression patterns. The IL-2-induced expression of the RGS16 gene in T cells is suppressed by elevated cAMP, whereas the RGS2 gene shows a reciprocal pattern of regulation by these stimuli. Because the mitogen and cytokine receptors that trigger expression of RGS2 and RGS16 in T cells do not activate heterotrimeric G proteins, these RGS proteins and the G proteins that they regulate may play a heretofore unrecognized role in T cell functional responses to Ag and cytokine activation.

The number and affinity of GABA(B) receptors (assayed by the specific antagonist [H-3]CGP54626A) was unchanged when compared in carefully washed cerebrocortical membranes from young (12-day-old) and adult (90-day-old) rats. In contrast, high-affinity GTPase activity, both basal and baclofen-stimulated was significantly higher (by 45% and 56%, respectively) in adult than in young rats. Similar results were obtained by concomitant determination of agonist (baclofen)-stimulated GTPgammaS binding. Under standard conditions, baclofen-stimulated GTPase activity was further considerably enhanced by exogenously added regulator of G protein function, RGS1, but not by RGS16. RGS16 was able to affect agonist-stimulated GTPase activity only in the presence of markedly increase substrate (GTP) concentrations. RGS1 alone slightly increased GTPase activity in adult rats, but neither RGS1 nor RGS16 influenced GTPase activity in membrane preparations isolated from young animals. These findings indicate increasing functional activity of trimeric G protein(s) involved in GABAergic transmission in the developing rat brain cortex and suggest a high potential of RGS1 I in regulation of high-affinity GTPase activity. (C) 2004 Elsevier B.V. All rights reserved.