An intrinsic guanine nucleotide exchange inhibitor in Gi2 alpha. Significance of G-protein self-suppression which antagonizes receptor signal.
The alpha subunit of Gi2 (Gi2 alpha) is a member of the heterotrimeric G protein family, which transduces receptor signals as a proto-oncogene product. We have found a novel self-suppressive region in Gi2 alpha near its C terminus. A polypeptide consisting of residues 338-352 of Gi2 alpha (Gi2 alpha-339-352) antagonizes receptor- and receptor peptide-stimulated Gi2 alpha activation, without affecting basal activity. Antagonism by Gi2 alpha-338-352 is attributable to an interaction with activated Gi2 alpha, which is not competitive with receptor polypeptides. Combined with the reports suggesting the presence of self-suppressive domains in a juxta-C-terminal portion of Gi2 alpha and G(o) alpha, this study supports the hypothesis that Gi2 alpha-338-352 constitutes an intrinsic guanine nucleotide exchange inhibitor, which in turn antagonizes receptor stimulation, suggesting that G proteins are activated by receptors through relaxation of a self-suppressive conformation.
Okamoto
T
T
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown.
Murayama
Y
Y
Strittmatter
S M
SM
Katada
T
T
Asano
S
S
Ogata
E
E
Nishimoto
I
I
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction
D006150:Guanine Nucleotides; D011956:Receptors, Cell Surface; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins