Reciprocal regulation of Gsα by palmitate and the βγ subunit
Hormonal activation of G s , the stimulatory regulator of adenylyl cyclase, promotes dissociation of α s from Gβγ, accelerates removal of covalently attached palmitate from the Gα subunit, and triggers release of a fraction of α s from the plasma membrane into the cytosol. To elucidate relations amo...
Gespeichert in:
Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1996-12, Vol.93 (25), p.14592-14597 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Hormonal activation of G s , the stimulatory regulator of adenylyl cyclase, promotes dissociation of α s from Gβγ, accelerates removal of covalently attached palmitate from the Gα subunit, and triggers release of a fraction of α s from the plasma membrane into the cytosol. To elucidate relations among these three events, we assessed biochemical effects in vitro of attached palmitate on recombinant α s prepared from Sf9 cells. In comparison to the unpalmitoylated protein (obtained from cytosol of Sf9 cells, treated with a palmitoyl esterase, or expressed as a mutant protein lacking the site for palmitoylation), palmitoylated α s (from Sf9 membranes, 50% palmitoylated) was more hydrophobic, as indicated by partitioning into TX-114, and bound βγ with 5-fold higher affinity. βγ protected GDP-bound α s , but not α s · GTP[γS], from depalmitoylation by a recombinant esterase. We conclude that βγ binding and palmitoylation reciprocally potentiate each other in promoting membrane attachment of α s and that dissociation of α s ·GTP from βγ is likely to mediate receptor-induced α s depalmitoylation and translocation of the protein to cytosol in intact cells. trimeric G proteins lipid modification membrane localization protein–protein interaction |
---|---|
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.93.25.14592 |