期刊论文详细信息
Cellular Physiology and Biochemistry
Downregulation of ClC-2 by JAK2
关键词: JAK2V617F;    Leptin;    Erythropoietin;    Cell volume regulation;    Chloride channels;   
DOI  :  10.1159/000178560
学科分类:分子生物学,细胞生物学和基因
来源: S Karger AG
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【 摘 要 】

JAK2 (Janus kinase-2) is activated by cell shrinkage and may thus participate in cell volume regulation. Cell volume regulatory ion channels include the small conductance Cl-channels ClC-2. The present study thus explored whether JAK2 influences ClC-2 activity. To this end, ClC-2 was expressed in Xenopus oocytes with or without wild type JAK2, active V617FJAK2 or inactive K882EJAK2 and the Cl channel activity determined by dual electrode voltage clamp. Expression of ClC-2 was followed by a marked increase of cell membrane conductance. The conductance was significantly decreased following coexpression of JAK2 or V617FJAK2, but not by coexpression of K882EJAK2. Exposure of the oocytes expressing ClC-2 together with V617FJAK2 to the JAK2 inhibitor AG490 (40 µM) resulted in a gradual increase of the conductance. According to chemiluminescence JAK2 decreased the channel protein abundance in the cell membrane. The decline of conductance in ClC-2 and V617FJAK2 coexpressing oocytes following inhibition of channel protein insertion by brefeldin A (5 µM) was similar in oocytes expressing ClC-2 with V617FJAK2 and oocytes expressing ClC-2 alone, indicating that V617FJAK2 might slow channel protein insertion into rather than accelerating channel protein retrieval from the cell membrane. In conclusion, JAK2 down-regulates ClC-2 activity and thus counteracts Cl-exit, an effect which may impact on cell volume regulation.

【 授权许可】

CC BY-NC-ND   

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