Protein tyrosine phosphatase 1B (PTP1B): A key regulator and therapeutic target in liver diseases

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摘要：

Phosphorylation of tyrosine residues within proteins, which is controlled by the reciprocal action of protein tyrosine kinases and protein tyrosine phosphatases, plays a key role in regulating almost all physiological responses. Therefore, it comes as no surprise that once the balance of tyrosine phosphorylation is disturbed, drastic effects can occur. Protein tyrosine phosphatase 1B (PTP1B), a classical non-transmembrane tyrosine phosphatase, is a pivotal regulator and promising drug target in type 2 diabetes and obesity. Recently it has received renewed attention in liver diseases and represents an intriguing opportunity as a drug target by modulating hepatocyte death and survival, hepatic lipogenesis and so on. Here, the multiple roles of PTP1B in liver diseases will be presented, with respect to liver regeneration, drug-induced liver disease, non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma.

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PTKs, protein tyrosine kinases PTPs, protein tyrosine phosphatases PTP1B, protein tyrosine phosphatase 1B NAFLD, non-alcoholic fatty liver disease HCC, hepatocellular carcinoma DSPs, dual specificity phosphatases LMW, low molecular weight RPTPs, transmembrane receptor-like PTPs NRPTPs, nonreceptor-like PTPs MKPs, mitogen-activated protein kinase phosphatases PRLs, pTyr-specific phosphatases of regenerating liver PIP3, phosphatidylinositol-(3,4,5)-triphosphate LMPTP, low molecular weight PTP PTPN1, protein tyrosine phosphatase non-receptor type1 ER, endoplasmic reticulum DISC, death-inducing signaling complex WT, wild-type ERK, extracellular signal regulated kinases NF-κB, nuclear factor κB TGF-β, transforming growth factor beta NOX, NADPH oxidase TNF-α, tumor necrosis factor-α IL-6, interleukin-6 STAT3, signal transducer and activator of transcription 3 HGF, hepatocyte growth factor EGF, epidermal growth factor PCNA, proliferating cell nuclear antigen JNK, c-Jun N-terminal kinase PH, partial hepatectomy KO, k