title: From signal transduction to signal interpretation: an alternative model for the molecular function of insulin receptor substrates.
abstract: The insulin receptor (IR) recruits adaptor proteins, so-called insulin receptor substrates (IRS), to connect with downstream signalling pathways. A family of IRS proteins was defined based on three major common structural elements: Amino-terminal PH and PTB domains that mediate protein-lipid or protein-protein interactions, mostly carboxy-terminal multiple tyrosine residues that serve as binding sites for proteins that contain one or more SH2 domains and serine/threonine-rich regions which may be recognized by negative regulators of insulin action. The current model for the role of IRS proteins therefore combines an adaptor function with the integration of mostly negative input from other signal transduction cascades allowing for modulation of signalling amplitude. In this review we propose an extended version of the adaptor model that can explain how signalling specificity could be implemented at the level of IRS proteins.
authors.affiliation: Endocrinology, Diabetes and Clinical Nutrition, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Boller
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Joblin
authors.forename: Linhua
authors.initials: L
authors.lastname: Xu
authors.forename: Flurin
authors.initials: F
authors.lastname: Item
authors.forename: Thomas
authors.initials: T
authors.lastname: Trüb
authors.forename: Nicola
authors.initials: N
authors.lastname: Boschetti
authors.forename: Giatgen A
authors.initials: GA
authors.lastname: Spinas
authors.forename: Markus
authors.initials: M
authors.lastname: Niessen
mesh_terms: D000818:Animals; D001665:Binding Sites; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D008954:Models, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D055504:Insulin Receptor Substrate Proteins; D014443:Tyrosine; D011972:Receptor, Insulin