Protein-tyrosine phosphatase 1B substrates and control of Metabolism

Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of several signaling networks that are implicated in human metabolic diseases such as diabetes and obesity. A growing body of evidence demonstrates that PTP1B displays exquisite substrate specificity. In this chapter we review mechanisms that regulate PTP1B-susbtrate interactions and highlight substrates that mediate PTP1B metabolic actions. PTP1B-substrate interactions are modulated by PTP1B subcellular location and numerous posttranslational modifications that regulate its activity such as oxidation, nitrosylation, sulfhydration, sumoylation, phosphorylation, and proteolysis. The metabolic actions of PTP1B are mediated by key physiological substrates that regulate insulin and leptin signaling, cell-cell communication, and endoplasmic reticulum (ER) stress response.