Insulin receptors and insulin receptor antibodies: structure-function relationships. 1982

S Jacobs, and P Cuatrecasas

The insulin receptor has been purified by affinity chromatography and studied by affinity-labelling techniques. It appears to be a disulphide-linked heterotetramer, (alpha beta)2, composed of two copies of a 135,000 Mr subunit (alpha), and two copies of a 90,000 Mr subunit (beta). Beta is readily proteolysed to generate a 45,000 Mr fragment (beta 1). Alpha, beta and beta 1 all contain sialic acid and are, therefore, probably all exposed on the external surface of the membrane. Although alpha is predominantly labelled in affinity-labelling studies, beta and beta 1 can also be labelled. Therefore, alpha, beta and beta 1 are all in proximity to the insulin-binding site and may contain part of the binding site. Antibodies have been prepared against the intact, purified receptor and against the isolated alpha subunit. Both antibodies directly interact with the insulin receptor as indicated by their ability to immunoprecipitate the receptor. Neither antibody, however, directly competes with insulin binding. Therefore, they are probably directed against regions of the receptor distinct from the insulin-binding site. In spite of this, these antibodies have a wide range of insulin-like activities.

UI MeSH Term Description Entries
D011972 Receptor, Insulin A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE. Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001323 Autoantibodies Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them. Autoantibody
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D046911 Macromolecular Substances Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure. Macromolecular Complexes,Macromolecular Compounds,Macromolecular Compounds and Complexes,Complexes, Macromolecular,Compounds, Macromolecular,Substances, Macromolecular

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