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

doi:10.1016/j.dci.2013.03.001

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	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
	Zhang, Jian 1,2; Chen, Ling 1,2; Sun, Li 1; Sun, L
	2013-06-01
发表期刊	DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
ISSN	0145-305X
卷号	40 期号:2 页码:103-111
文章类型	Article
摘要	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 degrees 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. (C) 2013 Elsevier Ltd. All rights reserved.; 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 degrees 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. (C) 2013 Elsevier Ltd. All rights reserved.
关键词	Protein Tyrosine Phosphatase Scophthalmus Maximus Immune Regulation Phagocytosis
学科领域	Immunology ; Zoology
DOI	10.1016/j.dci.2013.03.001
URL	查看原文
收录类别	SCI
语种	英语
WOS研究方向	Immunology ; Zoology
WOS类目	Immunology ; Zoology
WOS记录号	WOS:000320491100003
WOS关键词	PHOSPHOTYROSINE PHOSPHATASE ; CRYSTAL-STRUCTURE ; SCOPHTHALMUS-MAXIMUS ; LMW-PTP ; EXPRESSION ; GROWTH ; STIMULATION ; DEPHOSPHORYLATION ; PHOSPHORYLATION ; INACTIVATION
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
引用统计	被引频次：6[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/16521
专题	实验海洋生物学重点实验室
通讯作者	Sun, L
作者单位	1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
第一作者单位	实验海洋生物学重点实验室
推荐引用方式 GB/T 7714	Zhang, Jian,Chen, Ling,Sun, Li,et al. 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[J]. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY,2013,40(2):103-111.
APA	Zhang, Jian,Chen, Ling,Sun, Li,&Sun, L.(2013).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.DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY,40(2),103-111.
MLA	Zhang, Jian,et al."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".DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 40.2(2013):103-111.

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