title: Differential effect of pp120 on insulin endocytosis by two variant insulin receptor isoforms.
abstract: The insulin receptor is expressed as two variably spliced isoforms that differ by the absence (isoform A) or presence (isoform B) of a 12-amino acid sequence encoded by exon 11 at the carboxy terminus of the alpha-subunit. Coexpression of the A isoform and pp120, a substrate of the insulin receptor tyrosine kinase, in NIH 3T3 fibroblasts increased receptor A-mediated insulin endocytosis and degradation by two- to threefold compared with cells expressing receptors alone. Because B is the predominant isoform in the liver and binds insulin with lower affinity than A, we have examined the effect of pp120 on receptor B-mediated endocytosis. In contrast to isoform A, the effect of pp120 on isoform B-mediated insulin internalization and degradation in stably transfected NIH 3T3 cells was minimal.
authors.affiliation: Department of Pharmacology and Therapeutics, Medical College of Ohio, Toledo 43614, USA.
authors.forename: S
authors.initials: S
authors.lastname: Li Calzi
authors.forename: C V
authors.initials: CV
authors.lastname: Choice
authors.forename: S M
authors.initials: SM
authors.lastname: Najjar
mesh_terms: D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000378:metabolism*; D004705:Endocytosis; D005091:Exons; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D014644:Genetic Variation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D007328:Insulin; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse