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

Article ID	Journal	Published Year	Pages	File Type
5859066	Toxicology	2015	36 Pages	PDF

Abstract

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.

Keywords

APAP TGF-β ASO ERK ERS PP2A HFD LMW PCNA DSPs IRS Mitogen-activated protein kinase phosphatases MKPs STAT3 N-acetyl-p-benzoquinoneimine DISC HMGCS1 PTP1B nuclear factor erythroid-2-related factor 2 SnoN PIP3 ALF NAPQI HGF SREBP NF-κB PI3K IL-6 Jnk GSH EGF PTPN1 Nrf2 FAS NAFLD ACC BiP C/EBP homologous protein c-Jun N-terminal kinase HCC MAPK NOx antisense oligonucleotide PTKs PTPs ROS Proliferating Cell Nuclear Antigen Acetaminophen Endoplasmic reticulum stress acetyl-CoA carboxylase fatty acid synthase insulin receptor substrate NADPH oxidase interleukin-6 Liver regeneration Drug-induced liver disease Non-alcoholic fatty liver disease (NAFLD)non-alcoholic fatty liver disease Transforming Growth Factor Beta tumor necrosis factor-α CHOP Dual specificity phosphatases DILI high-fat diet Metabolic syndrome extracellular signal regulated kinases endoplasmic reticulum epidermal growth factor Hepatocyte growth factor TNF-α nuclear factor κB Phosphatase 2A Phosphatidylinositol 3-kinase signal transducer and activator of transcription 3 METS Acute liver failure knockout wild-type Partial hepatectomy low molecular weight Sterol regulatory element-binding protein Binding immunoglobulin Protein protein tyrosine phosphatases Protein tyrosine phosphatase 1B Protein tyrosine phosphatase 1B (PTP1B)Protein tyrosine kinases mitogen-activated protein kinase death-inducing signaling complex Hepatocellular carcinoma (HCC)Hepatocellular carcinoma Glutathione Reactive oxygen species insulin receptor insulin-like growth factor-I receptor