The receptor for insulin-like growth factor II mediates an insulin-like response.
Insulin-like growth factor II (IGF-II) shares sequence homology and predicted three-dimensional structure with insulin and IGF-I. IGF-II can bind, therefore, to a limited extent with the receptors for these two other hormones, as well as to a distinct receptor for IGF-II. Previous studies have been unable to attribute a particular response of IGF-II through its own receptor. In the present studies, the IGF-II receptor is shown to mediate the stimulation of glycogen synthesis in human hepatoma cells since: (i) IGF-II is found to be capable of stimulating a response at concentrations in which it would primarily interact with its own receptor; (ii) the response to IGF-II was not blocked by monoclonal antibodies which inhibit the responses of cells through the insulin and IGF-I receptors; and (iii) polyclonal antibodies to the IGF-II receptor were found to mimic the ability of IGF-II to stimulate glycogen synthesis. These results indicate that the IGF-II receptor mediates a particular biological response--stimulation of glycogen synthesis in hepatoma cells. Furthermore, a monovalent Fab fragment of the polyclonal antibody to the IGF-II receptor was also shown to stimulate glycogen synthesis in these cells. These data indicate that clustering of the IGF-II receptor is not required to stimulate a biological response.
Hari
J
J
Department of Pharmacology, Stanford University School of Medicine, CA 94305-5332.
Pierce
S B
SB
Morgan
D O
DO
Sara
V
V
Smith
M C
MC
Roth
R A
RA
D000911:Antibodies, Monoclonal; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D006003:Glycogen / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000276:immunology / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D007700:Kinetics; D008113:Liver Neoplasms; D011972:Receptor, Insulin / Q000502:physiology*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D007328:Insulin; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D006003:Glycogen; D011972:Receptor, Insulin