title: SmLMWPTP, a teleost low molecular weight protein tyrosine phosphatase, inhibits the immune response of peripheral blood leukocytes in a manner that depends on the conserved P-loop.
abstract: Protein tyrosine phosphatases (PTPs) are a family of enzymes that play a key role in cellular signal transduction. Low molecular weight PTPs (LMWPTPs) are a subfamily of PTPs that are characterized by the presence of a conserved phosphate-binding loop (P-loop) with the signature sequence of (V/I)CXGNXCRS. To date, very little study on teleost LMWPTPs has been documented, and, as a result, the function of LMWPTPs in fish is essentially unknown. In this study, we identified a LMWPTP from turbot (Scophthalmus maximus) and examined its biological activity and functionality. The turbot LMWPTP (SmLMWPTP) is composed of 158 residues and possesses a typical P-loop sequence in the form of (12)VCLGNICRS(20). Purified recombinant SmLMWPTP (rSmLMWPTP) exhibited apparent phosphatase activity, which was optimal at pH 5 and 50°C. The activity of SmLMWPTP was abolished when C13 and, in particular, R19 of the P-loop were mutated. SmLMWPTP expression was detected in a wide range of tissues and upregulated by bacterial and viral infection. Subcellular localization analysis showed that SmLMWPTP was secreted by peripheral blood leukocytes (PBL) into the extracellular milieu. When PBL were treated with rSmLMWPTP, the cells exhibited significant reductions in (i) proliferative and respiratory burst activity, (ii) expression levels of multiple immune relevant genes, and (iii) phagocytic activity. In contrast, the mutant SmLMWPTP bearing R19 mutation had no effect on PBL activity. Taken together, these results indicate that SmLMWPTP is a secreted PTP that exerts a negative regulatory effect on the innate immune response of PBL in a manner that depends on the structural integrity of the P-loop.
authors.affiliation: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Sun
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D020609:Edwardsiella tarda / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D029941:Fish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005412:Flatfishes / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions; D006863:Hydrogen-Ion Concentration; D007111:Immunity, Cellular; D007497:Iridoviridae / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009928:Organ Specificity; D010587:Phagocytosis; D021381:Protein Transport; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D029941:Fish Proteins; D017027:Protein Tyrosine Phosphatases