Replacement of insulin receptor tyrosine residues 1162 and 1163 does not alter the mitogenic effect of the hormone
- Institut National de la Sante et de la Recherche Medicale, Nice (France)
Chinese hamster ovary transfectants that express insulin receptors in which tyrosine residues 1162 and 1163 were replaced by phenylalanine exhibit a total inhibition of the insulin-mediated tyrosine kinase activity toward exogenous substrates; this latter activity is associated with total inhibition of the hypersensitivity reported for insulin in promoting 2-deoxyglucose uptake. The authors now present evidence that the twin tyrosines also control the insulin-mediated stimulation of glycogen synthesis. Surprisingly, this type of Chinese hamster ovary transfectant is as hypersensitive to insulin for its mitogenic effect as are Chinese hamster ovary cells expressing many intact insulin receptors. Such data suggest that (i) the insulin mitogenic effect routes through a different pathway than insulin uses to activate the transport and metabolism of glucose and (ii) the mitogenic effect of insulin is not controlled by the twin tyrosines. At the molecular level, the solubilized mutated receptor has not insulin-dependent tyrosine kinase activity, whereas this receptor displays measurable insulin-stimulated phosphorylation of its {beta} subunit in {sup 32}P-labeled cells. The authors therefore propose that the autocatalytic phosphorylating activity of the receptor reports a cryptic tyrosine kinase activity that cannot be visualized by the use of classical exogenous substrates.
- OSTI ID:
- 5547084
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:21; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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PHOSPHOTRANSFERASES
ENZYME ACTIVITY
RECEPTORS
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CELL PROLIFERATION
CHO CELLS
DNA REPLICATION
INHIBITION
INSULIN
MITOGENS
MUTATIONS
PHENYLALANINE
THYMIDINE
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MONOSACCHARIDES
NUCLEIC ACID REPLICATION
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NUCLEOTIDES
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ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PHOSPHORUS-GROUP TRANSFERASES
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550201* - Biochemistry- Tracer Techniques