Protein Phosphatase/PTP

The PTPs constitute a large family of enzymes with 107 members divided into 4 groups based on their protein sequences and functions. The major group is class I PTPs, which includes 99 members, and each member shares a conserved active site sequence (H/V)C(X)5R(S/T) with the cysteine as the catalytic residue in the dephosphorylation reaction. Class I is further divided into classic tyrosine-specific PTPs, and tyrosine and serine/threonine dual-specific phosphatases (DUSP), with 38 and 61 members, respectively. Classical tyrosine-specific PTPs are composed of 17 cytosolic PTPs and 21 trans-membrane receptor-like PTPs, and the DUSPs are further divided into MKP, Myotubularin, CDC14, Slingshot, PTEN, PRL, and atypical DSP subclasses. Class II PTP has only one member, the low molecular weight (LMW) PTP, and class III has three members, namely CDC25A, CDC25B, and CDC25C. Class II and class III PTPs also have catalytic cysteine residues. Class IV PTPs have 4 members with catalytic aspartic acid residues, which is in contrast to Class I, II, and III PTPs. Class IV PTPs activities also require the presence of a metal ion, suggesting they have unique evolution origins. PTP targets in the field are including PTP1B, SHP2, LYP, CD45, FAP-1, STEP, MKP-1, PRL, LMWPTP, CDC25, with a focus on their implications in human diseases. Protein tyrosine phosphatases (PTPs) are considered next-generation drug targets. For instance, PTP1B is a well-known targets of type 2 diabetes and obesity, and recent studies indicate that it is also a promising target for breast cancer. SHP2 is a bona-fide oncoprotein, mutations of which cause juvenile myelomonocytic leukemia, acute myeloid leukemia, and solid tumors.


1.He RJ,et al. Acta Pharmacol Sin. 2014;35(10):1227–1246.