A simple structure encodes G protein-activating function of the IGF-II/mannose 6-phosphate receptor.
The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/man6PR) can directly interact with and activate Gi-2, a GTP binding protein (G protein). We found that the segment of residues 2410-2423 in the human IGF-II/man6PR activates Gi-2 in a manner similar to G-coupled receptors. We observed a hierarchy of the segment action when tested on various G proteins, with an order of Gi-2 greater than Gi-1 approximately Gi-3 greater than Go. The segment had no effect on Gs or low molecular weight G proteins. The segment action depended on its primary structure and was potentiated when the segment was connected with a part of the receptor transmembrane region. Finally, the Gi-2-activating function of the human IGF-II/man6PR could be blocked by an antibody against the segment, indicating a critical role for this small region of the receptor.
Okamoto
T
T
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Katada
T
T
Murayama
Y
Y
Ui
M
M
Ogata
E
E
Nishimoto
I
I
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003593:Cytoplasm; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008360:Mannosephosphates; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000502:physiology*; D017451:Receptors, Somatomedin; D015398:Signal Transduction; D013002:Somatomedins / Q000502:physiology; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D008360:Mannosephosphates; D010446:Peptide Fragments; D010743:Phospholipids; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D008274:Magnesium