title: p66Shc, a multifaceted protein linking Erk signalling, glucose metabolism, and oxidative stress.
abstract: p66Shc, a 66 kDa proto-oncogene Src collagen homologue (Shc) adaptor protein, is classically known as a signalling protein implicated in receptor tyrosine kinase signal transduction. The p66Shc isoform exerts a physiologically relevant, inhibitory signalling effect on the Erk pathway in skeletal muscle myoblasts, which is necessary for actin cytoskeleton polymerization and normal glucose transport responses. More recently, p66Shc has been also identified as a sensor of oxidative stress-induced apoptosis and as a longevity protein in mammals, actions which require Ser36 phosphorylation of the protein and consequent accumulation of intracellular reactive oxygen species. Oxidative stress plays a key role in dysfunction of several organs and tissues, and this is of interest in metabolic diseases such as type 2 diabetes. Thus changes in p66Shc expression and/or function may play an important role in the pathogenesis of type 2 diabetes and potentially serve as an effective target for its treatment.
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari School of Medicine, Bari, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Natalicchio
authors.forename: Federica
authors.initials: F
authors.lastname: Tortosa
authors.forename: Sebastio
authors.initials: S
authors.lastname: Perrini
authors.forename: Luigi
authors.initials: L
authors.lastname: Laviola
authors.forename: Francesco
authors.initials: F
authors.lastname: Giorgino
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D000090063:Proto-Oncogene Mas; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose