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Involvement of phosphatidylcholine‐selective phospholipase C in activation of mitogen‐activated protein kinase pathways in imidazoline receptor antisera‐selected protein
Author(s) -
Li Fei,
Wu Ning,
Su RuiBin,
Zheng JianQuan,
Xu Bo,
Lu XinQiang,
Cong Bin,
Li Jin
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20806
Subject(s) - phospholipase c , moxonidine , imidazoline receptor , signal transduction , rilmenidine , mapk/erk pathway , chinese hamster ovary cell , protein kinase c , gq alpha subunit , biology , diacylglycerol kinase , receptor , chemistry , g protein , microbiology and biotechnology , biochemistry , pharmacology , agonist
Imidazoline receptor antisera‐selected protein (IRAS) is considered as a candidate for the I 1 ‐imidazoline receptor (I 1 R), but the signaling pathway mediated by IRAS remains unknown. In our study, the signal transduction pathways of IRAS were investigated in CHO cells stably expressing IRAS (CHO‐IRAS), and compared to the native I 1 R signaling pathways. Rilmenidine or moxonidine (10 nM–100 µM), I 1 R agonists, failed to stimulate [ 35 S]‐GTPγS binding in CHO‐IRAS cell membrane preparations, suggesting that G protein may not be involved in IRAS signaling pathway. However, incubation of CHO‐IRAS with rilmenidine or moxonidine for 5 min could induce an upregulation of phosphatidylcholine‐selective phospholipase C (PC‐PLC) activity, and an increase in the accumulation of diacylglycerol (DAG), the hydrolysate of PC‐PLC, in a concentration‐dependent manner. The elevated activation of PC‐PLC by rilmenidine or moxonidine (100 nM) could be blocked by efaroxan, a selective I 1 R antagonist. Cells treated with rilmenidine or moxonidine showed an increased level of extracellular signal‐regulated kinase (ERK) phosphorylation in a concentration‐dependent manner, which could be reversed by efaroxan or D609, a selective PC‐PLC inhibitor. These results suggest that the signaling pathway of IRAS in response to I 1 R agonists coupled with the activation of PC‐PLC and its downstream signal transduction molecule, ERK. These findings are similar to those in the signaling pathways of native I 1 R, providing some new evidence for the relationship between I 1 R and IRAS. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.