Ahnak protein activates protein kinase C (PKC) through dissociation of the PKC-protein phosphatase 2A complexopen access
- Authors
- Lee, IH[Lee, In Hye]; Lim, HJ[Lim, Hee Jung]; Yoon, S[Yoon, Suhyeon]; Seong, JK[Seong, Je Kyung]; Bae, DS[Bae, Duk Soo]; Rhee, SG[Rhee, Sue Goo]; Bae, YS[Bae, Yun Soo]
- Issue Date
- 7-Mar-2008
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.283, no.10, pp.6312 - 6320
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 283
- Number
- 10
- Start Page
- 6312
- End Page
- 6320
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/81835
- DOI
- 10.1074/jbc.M706878200
- ISSN
- 0021-9258
- Abstract
- We have previously reported that central repeated units (CRUs) of Ahnak act as a scaffolding protein networking phospholipase C gamma and protein kinase C (PKC). Here, we demonstrate that an Ahnak derivative consisting of four central repeated units binds and activates PKC-alpha 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-alpha 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-alpha activity is regulated through association with protein phosphatase 2A (PP2A). A co-immunoprecipitation assay indicated that the association of PKC-alpha 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.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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