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 p68/sup gag-ros/ has been constructed and expressed in Chinese hamster ovary (CHO) cells. The hybrid is processed normally into ..cap 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 resides of the hybrid ..beta..-subunit in vivo and the phosphorylation of an exogeneous 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 (/sup 3/H)thymidine into DNA, suggesting that the physiological response(s) mediated by ligand-activated protein-tyrosine kinases may utilize distinct intracellular mechanisms for postreceptor signaling
- Research Organization:
- Univ. of California, San Francisco (USA)
- OSTI ID:
- 5209820
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:15
- Country of Publication:
- United States
- Language:
- English
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INSULIN
MEMBRANE TRANSPORT
LABELLED COMPOUNDS
RECEPTORS
MOLECULAR STRUCTURE
CHO CELLS
IODINE 125
LIGANDS
METHIONINE
PHOSPHOTRANSFERASES
SULFUR 35
THYMIDINE
TRITIUM COMPOUNDS
AMINO ACIDS
ANIMAL CELLS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MEMBRANE PROTEINS
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDE HORMONES
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
SULFUR ISOTOPES
TRANSFERASES
550201* - Biochemistry- Tracer Techniques