Journal
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 37, Issue -, Pages 58-65Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2014.09.020
Keywords
PTP1B; Substrate; Obesity; Diabetes; ER stress; Pyruvate kinase
Categories
Funding
- Juvenile Diabetes Research Foundation
- American Diabetes Association
- National Institutes of Health [R56 DK084317, R01 DK090492, R01 DK095359, K99 DK100736]
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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. (C) 2014 Elsevier Ltd. All rights reserved.
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