Structure and function of the T-cell protein tyrosine phosphatase

Protein tyrosine phosphatases (PTP) have gained recognition as important regulators of mammalian cell signaling. Among these, T-cell protein tyrosine phosphatase (TC-PTP) participates in the negative regulation of surface receptor signaling. Indeed, several members of the Jak/Stat family of molecules involved in cytokine and hormone receptor signaling have now been identified as substrates for this phosphatase. In addition, TC-PTP has recently been shown to exert a positive regulatory role on cell proliferation through the NF-κB pathway. The analysis of TC-PTP null mice has revealed an important function for this enzyme in hematopoiesis and immune regulation, as demonstrated by the impaired lymphocyte response to mitogenic stimuli. In addition, these mice display an inflammatory phenotype characterized by elevated levels of IFN-γ. The recent description of the three-dimensional structure and functional domains of TC-PTP provides an opportunity for the design of specific inhibitors of this phosphatase with potential therapeutic implications.