A New Perspective on Appetite Control: Protein Tyrosine Phosphatase 1b (Ptp1b) Inactivation by Oxidative Phytochemicals

The leptin signal pathway relies on Janus kinase (JAK) and signal transducer/activator of transcription (STAT) proteins to propagate its signal. When leptin binds to its receptor, JAK2 is activated to phosphorylate leptin receptor and STAT3. The phosphorylated STAT3 dimerize and become capable of modulating gene expression in the nucleus. The JAK/STAT signal is modulated by a negative regulator, protein tyrosine phosphatase 1b (PTP1B), which dephosphorylates STAT3 and thus renders STAT3 back to its ground state [3,4]. Incidentally, insulin signal is also modulated by PTP1B. Insulin receptor activation results in phosphorylation on insulin receptor itself and its substrate, insulin receptor substrate (IRS). Both insulin receptor and IRS are modulated by PTP1B. Therefore, a potent PTP1B inhibitor has been proposed as a dual function inhibitor for treating obesity (leptin pathway) and diabetes (insulin pathway), as illustrated in Figure 2.