Guanosine 5'-(gamma-thio) triphosphate (GTP gamma S) inhibits phosphorylation of insulin receptor and a novel GTP-binding protein, Gir, from human placenta.
A novel 66 kDa GTP-binding protein, designated Gir, has been partially purified along with insulin receptor (IR) from human placenta. This protein binds 8-azido-GTP, is ADP-ribosylated by pertussis toxin, phosphorylated by IR tyrosine kinase and cross-reacts with antibodies against synthetic peptides from the GTP-binding domain of Gz alpha(P960). Phosphorylation of IR-beta subunit and Gir by IR tyrosine kinase was almost completely inhibited by 100 microM GTP gamma S, > 75% by 50 microM and 20-30% by 1 microM, while GDP at these concentrations had no significant effect on the phosphorylation. IR tyrosine kinase phosphorylated Gir at the tyrosine residues. These studies indicate regulation of IR tyrosine kinase activity by guanosine phosphates and involvement of Gir in insulin action.
Srivastava
S K
SK
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555.
Varma
T K
TK
Sinha
A C
AC
Singh
U S
US
D000595:Amino Acid Sequence; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011233:Precipitin Tests; D011247:Pregnancy; D011972:Receptor, Insulin / Q000187:drug effects* / Q000378:metabolism
D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011972:Receptor, Insulin; D019204:GTP-Binding Proteins