title: Tyr624 and Tyr628 in insulin receptor substrate-2 mediate its association with the insulin receptor.
abstract: In addition to the pleckstrin homology domain and the phosphotyrosine binding domain in insulin receptor substrate (IRS)-1 and IRS-2, a region between amino acids 591 and 786 in IRS-2 (IRS-2-(591-786)) binds to the insulin receptor. Based on peptide competition studies, this region interacts with the phosphorylated regulatory loop of the insulin receptor; we designate this region the kinase regulatory loop binding (KRLB) domain. Two tyrosine residues in the KRLB domain at positions 624 and 628 are crucial for this interaction. Phosphorylation of tyrosine residues in the KRLB domain by the insulin receptor inhibits the binding to the receptor. These results reveal a novel mechanism regulating the interaction of the insulin receptor and IRS-2 that may distinguish the signal of IRS-2 from IRS-1.
authors.affiliation: INSERM U145, Avenue de Valombrose, 06107 Nice Cedex 2, France.
authors.forename: D
authors.initials: D
authors.lastname: Sawka-Verhelle
authors.forename: V
authors.initials: V
authors.lastname: Baron
authors.forename: I
authors.initials: I
authors.lastname: Mothe
authors.forename: C
authors.initials: C
authors.lastname: Filloux
authors.forename: M F
authors.initials: MF
authors.lastname: White
authors.forename: E
authors.initials: E
authors.lastname: Van Obberghen
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D014443:Tyrosine; D011972:Receptor, Insulin