Heterologous transmembrane signaling by a human insulin receptor-v-ros hybrid in Chinese hamster ovary cells.
A hybrid receptor molecule composed of the extracellular ligand-binding domain of the human insulin receptor and the transmembrane and cytoplasmic (protein-tyrosine kinase) domains of the chicken sarcoma virus UR2 transforming protein p68gag-ros has been constructed and expressed in Chinese hamster ovary (CHO) cells. The hybrid is processed normally into alpha and hybrid beta subunits, is expressed on the cell surface at high levels, and binds insulin with near-wild-type affinity. Furthermore, insulin stimulates the phosphorylation on tyrosine residues of the hybrid beta subunit in vivo and the phosphorylation of an exogenous substrate [poly(Glu,Tyr)] in vitro. Thus the hybrid is capable of heterologous transmembrane signaling. However, the hybrid mediates neither the insulin-activated uptake of 2-deoxyglucose nor the incorporation of [3H]thymidine into DNA, suggesting that the physiological response(s) mediated by ligand-activated protein-tyrosine kinases may utilize distinct intracellular mechanisms for postreceptor signaling.
Ellis
L
L
Morgan
D O
DO
Jong
S M
SM
Wang
L H
LH
Roth
R A
RA
Rutter
W J
WJ
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D046911:Macromolecular Substances; D009856:Oncogene Proteins, Viral / Q000235:genetics; D010053:Ovary / Q000378:metabolism; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics; D013936:Thymidine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007328:Insulin; D046911:Macromolecular Substances; D009856:Oncogene Proteins, Viral; D003847:Deoxyglucose; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D013936:Thymidine