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

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dc.contributor.authorLee, In Hye-
dc.contributor.authorLim, Hee Jung-
dc.contributor.authorYoon, Suhyeon-
dc.contributor.authorSung, Je Kyeong-
dc.contributor.authorBae, Duk Soo-
dc.contributor.authorRhee, Sue Goo-
dc.contributor.authorBae, Yun Soo-
dc.date.accessioned2009-08-25T07:34:37Z-
dc.date.available2009-08-25T07:34:37Z-
dc.date.issued2008-
dc.identifier.citationJ. Biol. Chem. 283, 6312-6320en
dc.identifier.issn0021-9258-
dc.identifier.urihttps://hdl.handle.net/10371/7776-
dc.description.abstractWe 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.en
dc.description.sponsorshipThis work was supported in part by the National Core Research Center program
of the Ministry of Science and Technology/Korea Science and Engineering
Foundation (Grant R15-2006-020-00000-0) through the Center for
Cell Signaling and Drug Discovery Research at Ewha Womans University,
Basic Research Program of the Korea Science and Engineering Foundation
Grant RO1-2005-000-10480-0 (to Y. S. B.), and 21C Frontier Functional Proteomics
Projects Grant FPR0502-470 (to S. G. R.).
en
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.titleAhnak Protein Activates Protein Kinase C (PKC) through Dissociation of the PKC-Protein Phosphatase 2A Complexen
dc.typeArticleen
dc.contributor.AlternativeAuthor이인혜-
dc.contributor.AlternativeAuthor임희정-
dc.contributor.AlternativeAuthor윤수현-
dc.contributor.AlternativeAuthor성제경-
dc.contributor.AlternativeAuthor배덕수-
dc.contributor.AlternativeAuthor이수구-
dc.contributor.AlternativeAuthor배윤수-
dc.identifier.doi10.1074/jbc.M706878200-
Appears in Collections:
College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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