Loss of C-terminal α-helix decreased SDF-1α-mediated signaling and chemotaxis without influencing CXCR4 internalization

查看全文 作　　者：Shao-[1]huiCAI;[2]YiTAN;Xian-[1]daREN;Xiao-[1]hongLI;Shao-[2]xiCAI;[3]JunDU

机构地区：[1]DepartmentofClinicalPharmacologyPharmacySchoolofJi-nanUniversity,Guangzhou510612;[2]CollegeofBioengineering,KeyLaboratoryforBiomechanics&TissueEngineeringoftheStateMinistryofEducation,ChongqingUniversity,Chongqing400044;[3]DepartmentofMedicalTechnology,NagoyaUniversitySchoolofHealthSciences,Aichi461-8673,Japan

出　　处：《Acta Pharmacologica Sinica》索引2004年第25卷第2期,共9页

基　　金：Project supported by the National Natural Science Foundation of China (No 30271519 ) ;Visiting Scholar Foundation of Key Lab of the State Ministry of Education in Chongqing University. 摘　　要：AIM: To investigate the possibility that a novel α-helix-defective mutant of stromal cell-derived factor-1α (SDF- 1α) (SDF-1/54R) acts as an antagonist of CXC chemokine receptor 4 (CXCR4). METHODS: According to the genetic sequence of natural SDF-1α, a recombinant α-helix-defective mutant of SDF-1α was designed and some biologic characteristics of this mutant were demonstrated. The migration of Jurkat cells was assessed with chemo- tactic assay. ERK phosphorylation was analyzed by Western blot with a specific anti-phospho-ERK1/2 antibody. Intracellular calcium influx was examined by flow cytometer with a calcium indicator dye Fluo-3AM. The CXCR4 on the cell surface was detected by flow cytometer with a PE conjoined anti-human CXCR4 antibody. RESULTS: Compared with native SDF-1α, SDF-1/54R displayed apparent decrease in chemotactic ability, ERK1/2 activation, and intracellular calcium influx in Jurkat cells. However, the binding to CXCR4 and inducing CXCR4 internalization of SDF-1/54R did not change outstandingly. Moreover, a competitive inhibitory effect of SDF-1/54R on the migration of Jurkat cells induced by native SDF-1α was confirmed. CONCLUSION: α-helix-defective mutant of SDF-1α, SDF-1/54R that remained both the N-terminus and the central β-sheet region, decreased SDF-1α-medi- ated signaling and chemotaxis but did not influence CXCR4 internalization, which suggested that SDF-1/54R might be developed as an anti-CHIV inhibitor with high biological potency and low side-effect. 关键词：基质细胞源因子-1α 信号调节趋药性基因突变 CXC化学运动受体4 基因序列分析聚合酶链反应

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Loss of C-terminal α-helix decreased SDF-1α-mediated signaling and chemotaxis without influencing CXCR4 internalization

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