Replacement of insulin receptor tyrosine residues 1162 and 1163 does not alter the mitogenic effect of the hormone

Journal Article · Tue Nov 01 04:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.21.8032· OSTI ID:5547084

Debant, A; Clauser, E; Ponzio, G; Filloux, C; Auzan, C; Contreres, J O; Rossi, B ^[1]

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1. 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), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:21; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
AMINO ACIDS
ANIMAL CELLS
AZINES
CARBOHYDRATES
CARBOXYLIC ACIDS
CELL PROLIFERATION
CHEMICAL REACTIONS
CHO CELLS
DNA REPLICATION
ENZYME ACTIVITY
ENZYMES
GLUCOSE
HETEROCYCLIC COMPOUNDS
HEXOSES
HORMONES
HYDROGEN COMPOUNDS
HYDROXY ACIDS
INHIBITION
INSULIN
MEMBRANE PROTEINS
MITOGENS
MONOSACCHARIDES
MUTATIONS
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PHENYLALANINE
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
PYRIMIDINES
RECEPTORS
RIBOSIDES
SACCHARIDES
THYMIDINE
TRANSFERASES
TRITIUM COMPOUNDS
TYROSINE
UPTAKE