title: Protein-tyrosine phosphatase 1B substrates and metabolic regulation.
abstract: Metabolic homeostasis requires integration of complex signaling networks which, when deregulated, contribute to metabolic syndrome and related disorders. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as a key regulator of signaling networks that are implicated in metabolic diseases such as obesity and type 2 diabetes. In this review, we examine mechanisms that regulate PTP1B-substrate interaction, enzymatic activity and experimental approaches to identify PTP1B substrates. We then highlight findings that implicate PTP1B in metabolic regulation. In particular, insulin and leptin signaling are discussed as well as recently identified PTP1B substrates that are involved in endoplasmic reticulum stress response, cell-cell communication, energy balance and vesicle trafficking. In summary, PTP1B exhibits exquisite substrate specificity and is an outstanding pharmaceutical target for obesity and type 2 diabetes.
authors.affiliation: Department of Nutrition, University of California Davis, One Shields Ave, Davis, CA 95616, United States.
authors.forename: Jesse
authors.initials: J
authors.lastname: Bakke
authors.affiliation: Department of Nutrition, University of California Davis, One Shields Ave, Davis, CA 95616, United States; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, United States; Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, United States. Electronic address: fghaj@ucdavis.edu.
authors.forename: Fawaz G
authors.initials: FG
authors.lastname: Haj
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D020738:Leptin / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013816:Thermodynamics
chemical_list: D020738:Leptin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Diabetes; ER stress; Obesity; PTP1B; Pyruvate kinase; Substrate