Insulin receptor monoclonal antibodies that mimic insulin action without activating tyrosine kinase.
HTC rat hepatoma cells were transfected with human insulin receptor cDNA to a level of 40,000 receptors/cell. In these cells, as well as in nontransfected cells, insulin stimulated the uptake of alpha-aminoisobutyric acid. Two monoclonal antibodies directed against the human insulin receptor alpha subunit, like insulin, stimulated amino acid uptake in transfected HTC cells, but not in nontransfected HTC cells. The antibodies, in contrast to insulin, failed to stimulate insulin receptor tyrosine kinase activity, both in intact transfected cells and in cell free extracts prepared from them. These data suggest, therefore, that activation of insulin receptor tyrosine kinase may not be an obligatory step in all of the transmembrane signaling mechanisms of the insulin receptor.
Hawley
D M
DM
Cell Biology Laboratory, Mount Zion Hospital and Medical Center, San Francisco, California 94120.
Maddux
B A
BA
Patel
R G
RG
Wong
K Y
KY
Mamula
P W
PW
Firestone
G L
GL
Brunetti
A
A
Verspohl
E
E
Goldfine
I D
ID
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D000621:Aminoisobutyric Acids; D000911:Antibodies, Monoclonal; D007328:Insulin; C100049:2-aminoisobutyric acid; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin