This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wilkes, M. C.
Right arrow Articles by Leof, E. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilkes, M. C.
Right arrow Articles by Leof, E. B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2003, p. 8878-8889, Vol. 23, No. 23
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.23.8878-8889.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cell-Type-Specific Activation of PAK2 by Transforming Growth Factor ß Independent of Smad2 and Smad3

Mark C. Wilkes, Stephen J. Murphy, Nandor Garamszegi, and Edward B. Leof*

Department of Biochemistry and Molecular Biology, Thoracic Diseases Research Unit, and Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester Minnesota 55905

Received 8 May 2003/ Returned for modification 10 June 2003/ Accepted 21 August 2003

Transforming growth factor ß (TGF-ß) causes growth arrest in epithelial cells and proliferation and morphological transformation in fibroblasts. Despite the ability of TGF-ß to induce various cellular phenotypes, few discernible differences in TGF-ß signaling between cell types have been reported, with the only well-characterized pathway (the Smad cascade) seemingly under identical control. We determined that TGF-ß receptor signaling activates the STE20 homolog PAK2 in mammalian cells. PAK2 activation occurs in fibroblast but not epithelial cell cultures and is independent of Smad2 and/or Smad3. Furthermore, we show that TGF-ß-stimulated PAK2 activity is regulated by Rac1 and Cdc42 and dominant negative PAK2 or morpholino antisense oligonucleotides to PAK2 prevent the morphological alteration observed following TGF-ß addition. Thus, PAK2 represents a novel Smad-independent pathway that differentiates TGF-ß signaling in fibroblast (growth-stimulated) and epithelial cell (growth-inhibited) cultures.

* Corresponding author. Mailing address: Stabile 858, Mayo Clinic, Rochester, MN 55905. Phone: (507) 284-5717. Fax: (507) 284-4521. E-mail: leof.edward{at}mayo.edu.

Molecular and Cellular Biology, December 2003, p. 8878-8889, Vol. 23, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.23.8878-8889.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kahlem, P., Newfeld, S. J. (2009). Informatics approaches to understanding TGF{beta} pathway regulation. Development 136: 3729-3740 [Abstract] [Full Text]  
  • Hubchak, S. C., Sparks, E. E., Hayashida, T., Schnaper, H. W. (2009). Rac1 promotes TGF-{beta}-stimulated mesangial cell type I collagen expression through a PI3K/Akt-dependent mechanism. Am. J. Physiol. Renal Physiol. 297: F1316-F1323 [Abstract] [Full Text]  
  • Rahimi, R. A., Andrianifahanana, M., Wilkes, M. C., Edens, M., Kottom, T. J., Blenis, J., Leof, E. B. (2009). Distinct Roles for Mammalian Target of Rapamycin Complexes in the Fibroblast Response to Transforming Growth Factor-{beta}. Cancer Res. 69: 84-93 [Abstract] [Full Text]  
  • Gamell, C., Osses, N., Bartrons, R., Ruckle, T., Camps, M., Rosa, J. L., Ventura, F. (2008). BMP2 induction of actin cytoskeleton reorganization and cell migration requires PI3-kinase and Cdc42 activity. J. Cell Sci. 121: 3960-3970 [Abstract] [Full Text]  
  • Liu, A. C., Gotlieb, A. I. (2008). Transforming Growth Factor-{beta} Regulates in Vitro Heart Valve Repair by Activated Valve Interstitial Cells. Am. J. Pathol. 173: 1275-1285 [Abstract] [Full Text]  
  • Shin, D.-M., Jeon, J.-H., Kim, C.-W., Cho, S.-Y., Lee, H.-J., Jang, G.-Y., Jeong, E. M., Lee, D.-S., Kang, J.-H., Melino, G., Park, S.-C., Kim, I.-G. (2008). TGF{beta} mediates activation of transglutaminase 2 in response to oxidative stress that leads to protein aggregation. FASEB J. 22: 2498-2507 [Abstract] [Full Text]  
  • Murphy, S. J., Shapira, K. E., Henis, Y. I., Leof, E. B. (2007). A Unique Element in the Cytoplasmic Tail of the Type II Transforming Growth Factor-beta Receptor Controls Basolateral Delivery. Mol. Biol. Cell 18: 3788-3799 [Abstract] [Full Text]  
  • Levy, L., Howell, M., Das, D., Harkin, S., Episkopou, V., Hill, C. S. (2007). Arkadia Activates Smad3/Smad4-Dependent Transcription by Triggering Signal-Induced SnoN Degradation. Mol. Cell. Biol. 27: 6068-6083 [Abstract] [Full Text]  
  • Xie, S., Sukkar, M. B., Issa, R., Khorasani, N. M., Chung, K. F. (2007). Mechanisms of induction of airway smooth muscle hyperplasia by transforming growth factor-beta. Am. J. Physiol. Lung Cell. Mol. Physiol. 293: L245-L253 [Abstract] [Full Text]  
  • Suzuki, K., Wilkes, M. C., Garamszegi, N., Edens, M., Leof, E. B. (2007). Transforming Growth Factor {beta} Signaling via Ras in Mesenchymal Cells Requires p21-Activated Kinase 2 for Extracellular Signal-Regulated Kinase-Dependent Transcriptional Responses. Cancer Res. 67: 3673-3682 [Abstract] [Full Text]  
  • Sun, Y., Ding, L., Zhang, H., Han, J., Yang, X., Yan, J., Zhu, Y., Li, J., Song, H., Ye, Q. (2006). Potentiation of Smad-mediated transcriptional activation by the RNA-binding protein RBPMS. Nucleic Acids Res 34: 6314-6326 [Abstract] [Full Text]  
  • Menoret, A., Myers, L. M., Lee, S.-J., Mittler, R. S., Rossi, R. J., Vella, A. T. (2006). TGFbeta Protein Processing and Activity through TCR Triggering of Primary CD8+ T Regulatory Cells. J. Immunol. 177: 6091-6097 [Abstract] [Full Text]  
  • Seoane, J. (2006). Escaping from the TGF{beta} anti-proliferative control. Carcinogenesis 27: 2148-2156 [Abstract] [Full Text]  
  • Wang, S. E., Shin, I., Wu, F. Y., Friedman, D. B., Arteaga, C. L. (2006). HER2/Neu (ErbB2) Signaling to Rac1-Pak1 Is Temporally and Spatially Modulated by Transforming Growth Factor {beta}. Cancer Res. 66: 9591-9600 [Abstract] [Full Text]  
  • Wilkes, M. C., Leof, E. B. (2006). Transforming Growth Factor beta Activation of c-Abl Is Independent of Receptor Internalization and Regulated by Phosphatidylinositol 3-Kinase and PAK2 in Mesenchymal Cultures. J. Biol. Chem. 281: 27846-27854 [Abstract] [Full Text]  
  • Henderson, N. C., Mackinnon, A. C., Farnworth, S. L., Poirier, F., Russo, F. P., Iredale, J. P., Haslett, C., Simpson, K. J., Sethi, T. (2006). Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc. Natl. Acad. Sci. USA 103: 5060-5065 [Abstract] [Full Text]  
  • Zhu, Q., Pearson-White, S., Luo, K. (2005). Requirement for the SnoN Oncoprotein in Transforming Growth Factor {beta}-Induced Oncogenic Transformation of Fibroblast Cells. Mol. Cell. Biol. 25: 10731-10744 [Abstract] [Full Text]  
  • Wilkes, M. C., Mitchell, H., Penheiter, S. G., Dore, J. J., Suzuki, K., Edens, M., Sharma, D. K., Pagano, R. E., Leof, E. B. (2005). Transforming Growth Factor-{beta} Activation of Phosphatidylinositol 3-Kinase Is Independent of Smad2 and Smad3 and Regulates Fibroblast Responses via p21-Activated Kinase-2. Cancer Res. 65: 10431-10440 [Abstract] [Full Text]  
  • Hirschberg, R. (2005). What Benjamin Babington, William Osler, Frederick Weber, and Henri Rendu did not know. Cardiovasc Res 68: 180-182 [Full Text]  
  • Levy, L., Hill, C. S. (2005). Smad4 Dependency Defines Two Classes of Transforming Growth Factor {beta} (TGF-{beta}) Target Genes and Distinguishes TGF-{beta}-Induced Epithelial-Mesenchymal Transition from Its Antiproliferative and Migratory Responses. Mol. Cell. Biol. 25: 8108-8125 [Abstract] [Full Text]  
  • Moustakas, A., Heldin, C.-H. (2005). Non-Smad TGF-{beta} signals. J. Cell Sci. 118: 3573-3584 [Abstract] [Full Text]  
  • Barrios-Rodiles, M., Brown, K. R., Ozdamar, B., Bose, R., Liu, Z., Donovan, R. S., Shinjo, F., Liu, Y., Dembowy, J., Taylor, I. W., Luga, V., Przulj, N., Robinson, M., Suzuki, H., Hayashizaki, Y., Jurisica, I., Wrana, J. L. (2005). High-Throughput Mapping of a Dynamic Signaling Network in Mammalian Cells. Science 307: 1621-1625 [Abstract] [Full Text]  
  • Wang, S., Wilkes, M. C., Leof, E. B., Hirschberg, R. (2005). Imatinib mesylate blocks a non-Smad TGF-{beta} pathway and reduces renal fibrogenesis in vivo. FASEB J. 19: 1-11 [Abstract] [Full Text]  
  • Kaivo-Oja, N., Mottershead, D. G., Mazerbourg, S., Myllymaa, S., Duprat, S., Gilchrist, R. B., Groome, N. P., Hsueh, A. J., Ritvos, O. (2005). Adenoviral Gene Transfer Allows Smad-Responsive Gene Promoter Analyses and Delineation of Type I Receptor Usage of Transforming Growth Factor-{beta} Family Ligands in Cultured Human Granulosa Luteal Cells. J. Clin. Endocrinol. Metab. 90: 271-278 [Abstract] [Full Text]  
  • Nicolas, F. J., De Bosscher, K., Schmierer, B., Hill, C. S. (2004). Analysis of Smad nucleocytoplasmic shuttling in living cells. J. Cell Sci. 117: 4113-4125 [Abstract] [Full Text]  
  • Murphy, S. J., Dore, J. J. E., Edens, M., Coffey, R. J., Barnard, J. A., Mitchell, H., Wilkes, M., Leof, E. B. (2004). Differential Trafficking of Transforming Growth Factor-{beta} Receptors and Ligand in Polarized Epithelial Cells. Mol. Biol. Cell 15: 2853-2862 [Abstract] [Full Text]  
  • Mazerbourg, S., Klein, C., Roh, J., Kaivo-Oja, N., Mottershead, D. G., Korchynskyi, O., Ritvos, O., Hsueh, A. J. W. (2004). Growth Differentiation Factor-9 Signaling Is Mediated by the Type I Receptor, Activin Receptor-Like Kinase 5. Mol. Endocrinol. 18: 653-665 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»