Phosphorylation on TRPV4 Serine Residue 824 Enhances Its Association with PGM1  

作　　者：Sung Hwa Shin Eun Jeoung Lee Sunghee Hyun Sang Sun Kang Sung Hwa Shin;Eun Jeoung Lee;Sunghee Hyun;Sang Sun Kang(Department of Biology Education, Chungbuk National University, Cheongju, Republic of Korea;Department of Internal Medicine, Chungbuk National University, Cheongju, Republic of Korea;Department of Biomedical Laboratory Science, Eulji University, Daejeon, Republic of Korea)

机构地区：[1]Department of Biology Education, Chungbuk National University, Cheongju, Republic of Korea [2]Department of Internal Medicine, Chungbuk National University, Cheongju, Republic of Korea [3]Department of Biomedical Laboratory Science, Eulji University, Daejeon, Republic of Korea

出　　处：《American Journal of Molecular Biology》2016年第1期33-44,共12页美国分子生物学期刊（英文）

摘　　要：The TRPV4 cation channel is expressed in a broad range of tissues and participates in the generation of a Ca²⁺ signal and/or depolarization of membrane potential. Here, human phosphoglucomutase- 1 (PGM1), an enzyme that converts glucose-6 phosphate to glucose-1 phosphate in the glycolysis pathway, as the first auxiliary protein of TRPV4 Ca²⁺ channels, is identified with yeast two hybrid system, coimmunoprecipitation, confocal microscopy, and GST pull-down assays. TRPV4 forms a complex with PGM1 through its C-terminal cytoplasmic domain. Because it is demonstrated that TRPV4 serine residue 824 (S824) is phosphorylated by serum/glucocorticoid regulated kinase 1, we elucidate the effect of TRPV4 S824 phosphorylation on TRPV association with PGM1. Even an inactivated mutant version of TRPV4, S824A, exhibited a decreased ability to bind PGM1, an activated phosphomimetic mutant version of TRPV4, S824D, exhibited enhanced binding to PGM1. Thus, formation of the TRPV4/PGM1 complex and localization of this complex to the plasma membrane appear to be regulated by the phosphorylation status of residue S824 in TRPV4. The newly identified interactor of TRPV4 may help the molecular pathways modulating transport activity or glucose metabolism, respectively.The TRPV4 cation channel is expressed in a broad range of tissues and participates in the generation of a Ca²⁺ signal and/or depolarization of membrane potential. Here, human phosphoglucomutase- 1 (PGM1), an enzyme that converts glucose-6 phosphate to glucose-1 phosphate in the glycolysis pathway, as the first auxiliary protein of TRPV4 Ca²⁺ channels, is identified with yeast two hybrid system, coimmunoprecipitation, confocal microscopy, and GST pull-down assays. TRPV4 forms a complex with PGM1 through its C-terminal cytoplasmic domain. Because it is demonstrated that TRPV4 serine residue 824 (S824) is phosphorylated by serum/glucocorticoid regulated kinase 1, we elucidate the effect of TRPV4 S824 phosphorylation on TRPV association with PGM1. Even an inactivated mutant version of TRPV4, S824A, exhibited a decreased ability to bind PGM1, an activated phosphomimetic mutant version of TRPV4, S824D, exhibited enhanced binding to PGM1. Thus, formation of the TRPV4/PGM1 complex and localization of this complex to the plasma membrane appear to be regulated by the phosphorylation status of residue S824 in TRPV4. The newly identified interactor of TRPV4 may help the molecular pathways modulating transport activity or glucose metabolism, respectively.

关 键 词：Membrane Localization Phosphoglucomutase1 PHOSPHORYLATION Protein-Protein Interaction TRPV4 

分 类 号：R36[医药卫生—病理学]