Protein tyrosine phosphatases are a class of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine (pTyr) phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular localization, affect protein stability, and regulate enzyme activity. As a result, maintaining an appropriate level of protein tyrosine phosphorylation is essential for various cellular functions. Tyrosine-specific protein phosphatases catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation, transformation, and synaptic plasticity. PTP1B is an intracellular PTP located in the endoplasmic reticulum and expressed in various tissues of the human body; it maintains the balance of tyrosine protein phosphorylation with protein tyrosine kinase (Protein Tyrosine Kinases, PTK), and participates in cells. Signal transduction, regulating cell growth, differentiation, metabolism, gene transcription and immune response. PTP1B belongs to the family of protein tyrosine phosphatases, which specifically hydrolyze aromatic phosphates, such as phosphates that phosphorylate phosphate residues on phosphotyrosyl (pTyr) residues, by tyrosine on the insulin receptor or its substrate. Rephosphorylation of residues, negative regulation of insulin signaling, PTP1B overexpression in tissue cells will reduce the activity of PTK, so that insulin receptors cannot bind to insulin, which in turn causes insulin resistance, and ultimately leads to type 2 diabetes. PTP1B is widely present in many tissues of adipocytes, liver tissue cells, muscle tissue cells, and epithelial cells. Fluorescence immuno-in situ hybridization showed that PTP1B was mainly localized in the cytoplasmic endoplasmic reticulum, and 35 specific amino acids at the C-terminus were combined with the endoplasmic reticulum. The N-terminus contained cysteine and arginine residues. The catalytic center of the arginine residue faces the cytosol.
Figure 1. Protein tyrosine phosphatase 1, trimer + 3SO4 (red-green), Human
Individual PTPs might be expressed by all cell types, or their expression may be strictly tissue-specific. The majority of cells express 30% to 60% of all the PTPs, while hematopoietic and neuronal cells express a higher number of PTPs in comparison to other cell types. T cells and B cells of hematopoietic origin express around 60 to 70 different PTPs. The expression of several PTPS is restricted to hematopoietic cells, for instance, LYP, SHP1, CD45, and HePTP. The expression of PTPN5 is restricted to the brain. Differential expression of PTPN5 is observed in many brain regions, with no expression in the cerebellum.
PTP1B contains a catalytic domain consisting of 240 amino acid residues, of which 71 amino acid residues are highly conserved, and the catalytically active center is a sequence consisting of 11 amino acid residues, namely (I/V) HCXAGXXR ( S/T)G, in which the cysteine residue (Cys215) and the arginine residue (Ary221) play a crucial role in the activity of the PTP1B enzyme, and if substituted, will lose the catalytic activity of the enzyme.
PTP1B belongs to the family of protein tyrosine phosphatases. Together with protein tyrosine kinase (Protein Tyrosine Kinases, PTK), it maintains the balance of tyrosine protein phosphorylation, participates in cell signal transduction, regulates cell growth, differentiation and metabolism, gene transcription and immune response.
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