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Replacement of lysine residue 1030 in the putative ATP-binding region of the insulin receptor abolishes insulin- and antibody-stimulated glucose uptake and receptor kinase activity

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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To test whether the tyrosine kinase activity of the insulin receptor is crucial for insulin action, the authors have constructed mutations of the human insulin receptor at Lys-1030, which is in the presumed ATP-binding region. By using oligonucleotide-directed mutagenesis, this lysine residue was replaced with either methionine, arginine, or alanine. Chinese hamster ovary cells were transfected by mutant cDNAs and the expressed insulin receptors were characterized. They show here that none of these mutants exhibited insulin-activated autophosphorylation and kinase activity in vitro. They also do not mediate insulin- and antibody-stimulated uptake of 2-deoxyglucose. The tyrosine kinase activity is thus required for a key physiological response of insulin.
Research Organization:
Kumamoto Univ., Medical School, Japan
OSTI ID:
6371047
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:3; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALDEHYDES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOHYDRATES
CARBOXYLIC ACIDS
CHO CELLS
DAYS LIVING RADIOISOTOPES
DNA
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
EVEN-ODD NUCLEI
GLUCOSE
HEXOSES
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LYSINE
MAMMALS
MAN
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
MONOCLONAL ANTIBODIES
MONOSACCHARIDES
MUTAGENESIS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
RECOMBINANT DNA
SACCHARIDES
SULFUR 35
SULFUR ISOTOPES
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES