QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 10, 4765-4780, October 2005

This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: E05-03-0257v1 16/10/4765    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stasyk, T. Articles by Souchelnytskyi, S. Search for Related Content PubMed PubMed Citation Articles by Stasyk, T. Articles by Souchelnytskyi, S.

Phosphoproteome Profiling of Transforming Growth Factor (TGF)- Signaling: Abrogation of TGF1-dependent Phosphorylation of Transcription Factor-II-I (TFII-I) Enhances Cooperation of TFII-I and Smad3 in Transcription

Taras Stasyk ^* , Anna Dubrovska ^* , Marta Lomnytska ^* , Ihor Yakymovych ^*, Christer Wernstedt ^*, Carl-Henrik Heldin ^*, Ulf Hellman ^*, and Serhiy Souchelnytskyi ^*

^* Ludwig Institute for Cancer Research, Uppsala University, SE-751 24 Uppsala, Sweden; Department of Oncology and Medical Radiology, Lviv National Medical University, UA-79031 Lviv, Ukraine

Submitted March 28, 2005; Revised July 7, 2005; Accepted July 18, 2005
Monitoring Editor: Richard Assoian

Transforming growth factor- (TGF) signaling involves activation of a number of signaling pathways, several of which are controlled by phosphorylation events. Here, we describe a phosphoproteome profiling of MCF-7 human breast epithelial cells treated with TGF1. We identified 32 proteins that change their phosphorylation upon treatment with TGF1; 26 of these proteins are novel targets of TGF1. We show that Smad2 and Smad3 have different effects on the dynamics of TGF1-induced protein phosphorylation. The identified proteins belong to nine functional groups, e.g., proteins regulating RNA processing, cytoskeletal rearrangements, and proteasomal degradation. To evaluate the proteomics findings, we explored the functional importance of TGF1-dependent phosphorylation of one of the targets, i.e., transcription factor-II-I (TFII-I). We confirmed that TGF1 stimulated TFII-I phosphorylation at serine residues 371 and 743. Abrogation of the phosphorylation by replacement of Ser371 and Ser743 with alanine residues resulted in enhanced complex formation between TFII-I and Smad3, and enhanced cooperation between TFII-I and Smad3 in transcriptional regulation, as evaluated by a microarray-based measurement of expression of endogenous cyclin D2, cyclin D3, and E2F2 genes, and by a luciferase reporter assay. Thus, TGF1-dependent phosphorylation of TFII-I may modulate TGF signaling at the transcriptional level.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

Address correspondence to: Serhiy Souchelnytskyi (serhiy.souchelnytskyi{at}licr.uu.se).

This article has been cited by other articles:

				N.-O. Chimge, A. V. Makeyev, F. H. Ruddle, and D. Bayarsaihan Identification of the TFII-I family target genes in the vertebrate genome PNAS, July 1, 2008; 105(26): 9006 - 9010. [Abstract] [Full Text] [PDF]

				I. L.O. Buxton and D. Duan Cyclic GMP/Protein Kinase G Phosphorylation of Smad3 Blocks Transforming Growth Factor-{beta}-Induced Nuclear Smad Translocation: A Key Antifibrogenic Mechanism of Atrial Natriuretic Peptide Circ. Res., February 1, 2008; 102(2): 151 - 153. [Full Text] [PDF]

				L.-Y. Tang, N. Deng, L.-S. Wang, J. Dai, Z.-L. Wang, X.-S. Jiang, S.-J. Li, L. Li, Q.-H. Sheng, D.-Q. Wu, et al. Quantitative Phosphoproteome Profiling of Wnt3a-mediated Signaling Network: Indicating the Involvement of Ribonucleoside-diphosphate Reductase M2 Subunit Phosphorylation at Residue Serine 20 in Canonical Wnt Signal Transduction Mol. Cell. Proteomics, November 1, 2007; 6(11): 1952 - 1967. [Abstract] [Full Text] [PDF]