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

J. Biol. Chem., Vol. 281, Issue 32, 22624-22634, August 11, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/32/22624    most recent M601772200v1 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 Stefansson, B. Articles by Brautigan, D. L. Search for Related Content PubMed PubMed Citation Articles by Stefansson, B. Articles by Brautigan, D. L. Social Bookmarking                      What's this?

Protein Phosphatase 6 Subunit with Conserved Sit4-associated Protein Domain Targets IB^*

From the Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908

Protein Ser/Thr phosphatases compose a PPP family that includes type-2 PP2A, PP4, and PP6, each with essential functions. The human PP6 gene rescues sit4_ts mutants of Saccharomyces cerevisiae, and Sit4 phosphatase function depends on multiple Sit4-associated protein (SAP) subunits. We report here finding a SAPS sequence domain encoded in only a single gene each in Schizosaccharomyces pombe, Caenorhabditis elegans, and Drosophila but in three distinct open reading frames in Xenopus, Mus musculus, and Homo sapiens. The SAPS proteins are more divergent in sequence than PP6. Northern hybridization showed differential distribution of the human SAPS-related mRNA in multiple human tissues, named as PP6R1, PP6R2, and PP6R3. Antibodies were generated, distribution of endogenous PP6, PP6R1, PP6R2, and PP6R3 proteins was examined by immunoblotting, and the abundance of mRNA and protein in various tissues did not match. FLAG-tagged PP6R1 and PP6R2 expressed in HEK293 cells co-precipitated endogenous PP6, but not PP2A or PP4, showing specificity for recognition of phosphatases. The SAPS domain of PP6R1 alone was sufficient for association with PP6, and this predicts that conserved sequence motifs in the SAPS domain accounts for the specificity. FLAG-PP6R1 and FLAG-PP6R2 co-precipitated HA-IB. Knockdown of PP6 or PP6R1 but not PP6R3 with siRNA significantly enhanced degradation of endogenous IB in response to tumor necrosis factor-. The results show SAPS domain subunits recruit substrates such as IB as one way to determine specific functions for PP6.

Received for publication, February 23, 2006 , and in revised form, May 25, 2006.

Note Added in Proof—We recently produced by reverse transcription-PCR another PP6R3 from HeLa cells that does express as a FLAG-tagged protein in 293 cells.

^* This work supported in part by United States Public Health Service Grant CA-77584 (to D. L. B.). 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.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) DQ111954 [GenBank] .

The amino acid sequence of this protein can be accessed through NCBI Protein Database under NCBI accession number AAZ99639 [GenBank] .

¹ To whom correspondence should be addressed: Center for Cell Signaling University of Virginia School of Medicine P. O. Box 800577, West Complex MSB 7225 Charlottesville, VA 22908. Tel.: 434-924-5892; Fax: 434-243-2829; E-mail: db8g{at}virginia.edu.

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

This article has been cited by other articles:

				W. Wang, C. Cronmiller, and D. L. Brautigan Maternal Phosphatase Inhibitor-2 Is Required for Proper Chromosome Segregation and Mitotic Synchrony During Drosophila Embryogenesis Genetics, August 1, 2008; 179(4): 1823 - 1833. [Abstract] [Full Text] [PDF]

				T. D. Prickett, J. Ninomiya-Tsuji, P. Broglie, T. L. Muratore-Schroeder, J. Shabanowitz, D. F. Hunt, and D. L. Brautigan TAB4 Stimulates TAK1-TAB1 Phosphorylation and Binds Polyubiquitin to Direct Signaling to NF-{kappa}B J. Biol. Chem., July 11, 2008; 283(28): 19245 - 19254. [Abstract] [Full Text] [PDF]

				S. I. Kim, J. H. Kwak, L. Wang, and M. E. Choi Protein Phosphatase 2A Is a Negative Regulator of Transforming Growth Factor-{beta}1-induced TAK1 Activation in Mesangial Cells J. Biol. Chem., April 18, 2008; 283(16): 10753 - 10763. [Abstract] [Full Text] [PDF]

				T. D. Prickett and D. L. Brautigan Cytokine Activation of p38 Mitogen-Activated Protein Kinase and Apoptosis Is Opposed by alpha-4 Targeting of Protein Phosphatase 2A for Site-Specific Dephosphorylation of MEK3 Mol. Cell. Biol., June 15, 2007; 27(12): 4217 - 4227. [Abstract] [Full Text] [PDF]

				T. Kajino, H. Ren, S.-i. Iemura, T. Natsume, B. Stefansson, D. L. Brautigan, K. Matsumoto, and J. Ninomiya-Tsuji Protein Phosphatase 6 Down-regulates TAK1 Kinase Activation in the IL-1 Signaling Pathway J. Biol. Chem., December 29, 2006; 281(52): 39891 - 39896. [Abstract] [Full Text] [PDF]