GTP-binding protein-activator sequences in the insulin receptor.
Some functions of the insulin receptor (insR) are assumed to be mediated by pertussis toxin-sensitive Gi/G(o) proteins. Here we have located G-protein-activator domains in the cytoplasmic region of the human insR. We searched the sequence of insR and found three candidate regions at residues 1039-1061, 1147-1168 and 1325-1345, referred to as ISRP1, ISRP2 and ISRP3, respectively. Among them, the Gi/G(o)-activating function was observed only in peptide ISRP3. ISRP1 specifically activated Gs, whereas ISRP2 had no effect on G proteins. ISRP2 and ISRP3 contained five of six autophosphorylated tyrosine residues in insR. After tyrosine phosphorylation, ISRP2 showed specific Gi-activating function, and ISRP3 potentiated its ability and became capable of activating G proteins generally. This is the first study that specifies G-protein-activator domains in insR and describes their modification by autophosphorylation.
Okamoto
T
T
Department of Medicine, Harvard Medical School, Charlestown, MA 02129.
Okamoto
T
T
Murayama
Y
Y
Hayashi
Y
Y
Ogata
E
E
Nishimoto
I
I
D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D010446:Peptide Fragments; D011972:Receptor, Insulin; D019204:GTP-Binding Proteins