| First Author | Ransnäs LA | Year | 1988 |
| Journal | J Biol Chem | Volume | 263 |
| Issue | 33 | Pages | 17239-42 |
| PubMed ID | 3141418 | Mgi Jnum | J:166039 |
| Mgi Id | MGI:4839468 | Doi | 10.1016/s0021-9258(19)77824-7 |
| Citation | Ransnas LA, et al. (1988) Subunit dissociation is the mechanism for hormonal activation of the Gs protein in native membranes. J Biol Chem 263(33):17239-42 |
| abstractText | We have recently reported (Ransnas, L.A., and Insel, P.A. (1988) J. Biol. Chem. 263, 9482-9485) development of antipeptide antibodies to the alpha s protein of the stimulatory guanine nucleotide binding regulatory protein, Gs, and use of one of these antibodies, GS-1, to quantitate Gs levels in S49 lymphoma cell membranes. Another of these antibodies, termed GS-2, appears to detect only dissociated alpha s, but not the heterotrimer alpha s beta gamma. Using a competitive enzyme-linked immunosorbent assay, we have found that the guanine nucleotides GTP and guanosine 5'-O-(thiotriphosphate) (GTP gamma S) (but not GDP) and the beta-adrenergic receptor agonist isoproterenol activate Gs in native S49 cell membrane by subunit dissociation. Evidence for this includes detection of dissociated alpha s in membrane extracts and release of alpha s from S49 cell membranes treated with GTP gamma S or isoproterenol. Moreover, the estimates of apparent stoichiometry for this dissociation indicate that each beta-adrenergic receptor is able to activate greater than or equal to 100 molecules of Gs in native membranes. Thus, receptor-mediated dissociation of Gs is likely to be the major site of amplification of signal transduction by agonists active at hormone receptors that link to Gs. |
