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Ahnak Protein Activates Protein Kinase C (PKC) through Dissociation of the PKC-Protein Phosphatase 2A Complex

Cited 46 time in Web of Science Cited 49 time in Scopus
Authors
Lee, In Hye; Lim, Hee Jung; Yoon, Suhyeon; Sung, Je Kyeong; Bae, Duk Soo; Rhee, Sue Goo; Bae, Yun Soo
Issue Date
2008
Publisher
American Society for Biochemistry and Molecular Biology
Citation
J. Biol. Chem. 283, 6312-6320
Abstract
We have previously reported that central repeated units (CRUs) of Ahnak act as a scaffolding protein networking phospholipase C and protein kinase C (PKC). Here, we demonstrate that an Ahnak derivative consisting of four central repeated units binds and activates PKC- in a phosphatidylserine/1,2-dioleoyl-sn-glycerol-independent manner. Moreover, NIH3T3 cells expressing the 4 CRUs of Ahnak showed enhanced c-Raf, MEK, and Erk phosphorylation in response to phorbol 12-myristate 13-acetate (PMA) compared with parental cells. To evaluate the effect of loss-of-function of Ahnak in cell signaling, we investigated PKC activation and Raf phosphorylation in embryonic fibroblast cells (MEFs) of the Ahnak knock-out (Ahnak-/-) mouse. Membrane translocation of PKC- and phosphorylation of Raf in response to PMA or platelet-derived growth factor were decreased in Ahnak null MEF cells compared with wild type MEFs. Several lines of evidence suggest that PKC- activity is regulated through association with protein phosphatase 2A (PP2A). A co-immunoprecipitation assay indicated that the association of PKC- with PP2A was disrupted in NIH3T3 cells expressing 4 CRUs of Ahnak in response to PMA. Consistently, Ahnak null MEF cells stimulated by PMA showed enhanced PKC-PP2A complex formation, and add-back expression of Ahnak into Ahnak null MEF cells abolished the PKC-PP2A complex formation in response to PMA. These data indicate that Ahnak potentiates PKC activation through inhibiting the interaction of PKC with PP2A.
ISSN
0021-9258
Language
English
URI
https://hdl.handle.net/10371/7776
DOI
https://doi.org/10.1074/jbc.M706878200
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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