Interaction of the. alpha. beta. dimers of the insulin-like growth factor I receptor required for receptor autophosphorylation

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00215a008· OSTI ID:5527284

Tollesfsen, S E; Stoszek, R M; Thompson, K ^[1]

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1. Washington Univ. School of Medicine, St. Louis, MI (USA)

The authors have recently found that association of the two {alpha}{beta} dimers of the insulin-like growth factor I (IGF I) receptor is required for formation of a high-affinity binding site for IGF I. To determine the structural requirements for IGF I activated kinase activity, they have examined the effect of dissociation of the two {alpha}{beta} dimers of the IGF I receptor on {beta} subunit autophosphorylation. The {alpha}{beta} dimers formed after treatment with 2 mM dithiothreitol (DTT) at pH 8.75 for 5 min were separated from IGF I receptor remaining as tetramers after DTT treatment by fast protein liquid chromatography on a Superose 6 gel filtration column. Purification of the {alpha}{beta} dimers was confirmed by Western blot analysis using {sup 125}I-labeled {alpha}IR-3, a monoclonal antibody to the IGF I receptor. Autophosphorylation of the IGF I receptor ({alpha}{beta}){sub 2} tetramer, treated without DTT or remaining after DTT treatment, is stimulated 1.6-2.9-fold by IGF I. In contrast, autophosporylation of the {alpha}{beta} dimers incubated in the presence or absence of IGF I (100 ng/mL) does not occur. Both IGF I receptor dimers and tetramers exhibit similar kinase activities using the synthetic substrate Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly, indicating that the failure to detect autophosphorylation of the IGF I receptor dimers does not result from inactivation of the kinase by DTT treatment. They conclude that autophosphorylation of the IGF I receptor depends upon the interaction of the two {alpha}{beta} dimers.

• OSTI ID: 5527284
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 30:1; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
GROWTH FACTORS
HALIDES
HALOGEN COMPOUNDS
INACTIVATION
INORGANIC PHOSPHORS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODIDES
IODINE 125
IODINE COMPOUNDS
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MEMBRANE PROTEINS
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
PURIFICATION
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
SODIUM COMPOUNDS
SODIUM IODIDES
TRACER TECHNIQUES
TRANSFERASES