Heterologous transmembrane signaling by a human insulin receptor-v-ros hybrid in Chinese hamster ovary cells.
- 1 August 1987
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 84 (15) , 5101-5105
- https://doi.org/10.1073/pnas.84.15.5101
Abstract
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 medicates 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 kinase may utilize distinct intracellular mechanisms for postreceptor signaling.Keywords
This publication has 21 references indexed in Scilit:
- Acute insulin action requires insulin receptor kinase activity: introduction of an inhibitory monoclonal antibody into mammalian cells blocks the rapid effects of insulin.Proceedings of the National Academy of Sciences, 1987
- Linking functional domains of the human insulin receptor with the bacterial aspartate receptor.Proceedings of the National Academy of Sciences, 1986
- Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucoseCell, 1986
- Proto-oncogene c-ros codes for a molecule with structural features common to those of growth factor receptors and displays tissue specific and developmentally regulated expression.Molecular and Cellular Biology, 1986
- Mapping surface structures of the human insulin receptor with monoclonal antibodies: localization of main immunogenic regions to the receptor kinase domainBiochemistry, 1986
- Insulin action is blocked by a monoclonal antibody that inhibits the insulin receptor kinase.Proceedings of the National Academy of Sciences, 1986
- The human insulin receptor cDNA: The structural basis for hormone-activated transmembrane signallingCell, 1985
- Human insulin receptor and its relationship to the tyrosine kinase family of oncogenesNature, 1985
- Changes in protein phosphorylation in Rous sarcoma virus-transformed chicken embryo cells.Molecular and Cellular Biology, 1981
- DNA sequencing with chain-terminating inhibitorsProceedings of the National Academy of Sciences, 1977