HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 37, 26971-26980, September 14, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/37/26971    most recent M704059200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Longin, S. Articles by Janssens, V. Search for Related Content PubMed PubMed Citation Articles by Longin, S. Articles by Janssens, V. Social Bookmarking                      What's this?

Selection of Protein Phosphatase 2A Regulatory Subunits Is Mediated by the C Terminus of the Catalytic Subunit^*

Sari Longin, Karen Zwaenepoel, Justin V. Louis, Stephen Dilworth, Jozef Goris, and Veerle Janssens, A postdoctoral fellow of the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen¹

From the Protein Phosphorylation and Proteomics Laboratory, Department of Molecular Cell Biology, Faculty of Medicine, KULeuven, Herestraat 49 bus 901, B-3000 Leuven, Belgium and Department of Metabolic Medicine, Imperial College Faculty of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom

Protein phosphatase 2A (PP2A) is a family of multifunctional serine/threonine phosphatases all composed of a catalytic C, a structural A, and a regulatory B subunit. Assembly of the complex with the appropriate B subunit forms the key to the functional specificity and regulation of PP2A. Emerging evidence suggests a crucial role for methylation and phosphorylation of the PP2A C subunit in this process. In this study, we show that PP2A C subunit methylation was not absolutely required for binding the PR61/B' and PR72/B'' subunit families, whereas binding of the PR55/B subunit family was determined by methylation and the nature of the C-terminal amino acid side chain. Moreover mutation of the phosphorylatable Tyr³⁰⁷ or Thr³⁰⁴ residues differentially affected binding of distinct B subunit family members. Down-regulation of the PP2A methyltransferase LCMT1 by RNA interference gradually reduced the cellular amount of methylated C subunit and induced a dynamic redistribution of the remaining methylated PP2A_C between different PP2A trimers consistent with their methylation requirements. Persistent knockdown of LCMT1 eventually resulted in specific degradation of the PR55/B subunit and apoptotic cell death. Together these results establish a crucial foundation for understanding PP2A regulatory subunit selection.

Received for publication, May 16, 2007 , and in revised form, July 13, 2007.

^* This work was supported by grants from the "Geconcerteerde Onderzoeks-Acties" (Flemish government), IUAP "Interuniversity Attraction Poles" (Belgian Science Policy), and F.W.O.-Vlaanderen. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁵ Longin, S., Zwaenepoel, K., Martens, E., Louis, J. V., Rondelez, E., Goris, J., and Janssens, V. (2007) Exp. Cell Res., in press.

¹ To whom correspondence should be addressed: Afdeling Biochemie, Campus Gasthuisberg O&N1, Herestraat 49 bus 901, B-3000 Leuven, Belgium. Tel.: 32-16-330245; Fax: 32-16-345995; E-mail: Veerle.Janssens{at}med.kuleuven.be.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J.-M. Sontag, V. Nunbhakdi-Craig, L. Montgomery, E. Arning, T. Bottiglieri, and E. Sontag Folate Deficiency Induces In Vitro and Mouse Brain Region-Specific Downregulation of Leucine Carboxyl Methyltransferase-1 and Protein Phosphatase 2A B{alpha} Subunit Expression That Correlate with Enhanced Tau Phosphorylation J. Neurosci., November 5, 2008; 28(45): 11477 - 11487. [Abstract] [Full Text] [PDF]

				M. R. Junttila, S.-P. Li, and J. Westermarck Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival FASEB J, April 1, 2008; 22(4): 954 - 965. [Abstract] [Full Text] [PDF]

				D. Ricotta, J. Hansen, C. Preiss, D. Teichert, and S. Honing Characterization of a Protein Phosphatase 2A Holoenzyme That Dephosphorylates the Clathrin Adaptors AP-1 and AP-2 J. Biol. Chem., February 29, 2008; 283(9): 5510 - 5517. [Abstract] [Full Text] [PDF]