Role of Sst2 in modulating G protein-coupled receptor signaling

Sst2 formally acts as an inhibitor of G protein-coupled receptor signaling in yeast perhaps stabilizing a G protein/unactivated receptor complex. desTrp1, Ala3 alpha-factor (dTA-alpha f), normally a competitive antagonist, activated responses in an sst2 strain. The antagonist to agonist switch was consistent with an Sst2 effect on receptor/G protein coupling, but not with an Sst2 role in global reduction of signaling, Response to alpha-factor, assayed by growth arrest, was independent of level of expressed surface receptor over a 40-fold range in an SST2(+) strain, consistent with coupling of only a subset of receptors to G protein. In contrast, in an sst2 strain, response to alpha-factor was proportional to receptor expression, consistent with participation of all receptors in signaling. The wt alpha-factor receptor inhibited signaling in response to dTA-alpha f when introduced into a CKC4 chimeric receptor strain. The dominant-negative effect of the receptor might reflect sequestration of G protein. (C) 1996 Academic Press, Inc.