title: Phosphorylation of tyrosyl residues 350/354 of the beta-adrenergic receptor is obligatory for counterregulatory effects of insulin.
abstract: Insulin stimulates a loss of function and increased phosphotyrosine content of the beta 2-adrenergic receptor in intact cells, raising the possibility that the beta 2-receptor itself is a substrate for the insulin receptor tyrosine kinase. Phosphorylation of synthetic peptides corresponding to cytoplasmic domains of the beta 2-adrenergic receptor by the insulin receptor in vitro and peptide mapping of the beta 2-adrenergic receptor phosphorylated in vivo in cells stimulated by insulin reveal tyrosyl residues 350/354 and 364 in the cytoplasmic, C-terminal region of the beta 2-adrenergic receptor as primary targets. Mutation of tyrosyl residues 350, 354 (double mutation) to phenylalanine abolishes the ability of insulin to counterregulate beta-agonist stimulation of cyclic AMP accumulation. Phenylalanine substitution of tyrosyl reside 364, in contrast, abolishes beta-adrenergic stimulation itself.
authors.affiliation: Department of Molecular Pharmacology, State University of New York, Stony Brook 11794-8651, USA.
authors.forename: V
authors.initials: V
authors.lastname: Karoor
authors.forename: K
authors.initials: K
authors.lastname: Baltensperger
authors.forename: H
authors.initials: H
authors.lastname: Paul
authors.forename: M P
authors.initials: MP
authors.lastname: Czech
authors.forename: C C
authors.initials: CC
authors.lastname: Malbon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006224:Cricetinae; D015180:Electrophoresis, Gel, Two-Dimensional; D007328:Insulin / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D007328:Insulin; D010446:Peptide Fragments; D010748:Phosphopeptides; D018343:Receptors, Adrenergic, beta-2; D011972:Receptor, Insulin