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 Cheng, J.
Right arrow Articles by Su, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cheng, J.
Right arrow Articles by Su, B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2005, p. 5955-5964, Vol. 25, No. 14
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.14.5955-5964.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mip1, an MEKK2-Interacting Protein, Controls MEKK2 Dimerization and Activation

Jinke Cheng,1 Dongyu Zhang,1 Kihwan Kim,1 Yingxin Zhao,2 Yingming Zhao,2 and Bing Su1*

Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030,1 Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 752352

Received 19 December 2004/ Returned for modification 31 January 2005/ Accepted 26 April 2005

Mitogen-activated protein kinase (MAPK) cascades are central components of the intracellular signaling networks used by eukaryotic cells to respond to a wide spectrum of extracellular stimuli. An MAPK is activated by an MAPK kinase, which in turn is activated by an MAPK kinase kinase (MAP3K). However, little is known about the molecular aspects of the regulation and activation of large numbers of MAP3Ks that are crucial in relaying upstream receptor-mediated signals through the MAPK cascades to induce various physiological responses. In this study, we identified a novel MEKK2-interacting protein, Mip1, that regulates MEKK2 dimerization and activation by forming a complex with inactive and nonphosphorylated MEKK2. In particular, Mip1 prevented MEKK2 activation by blocking MEKK2 dimer formation, which in turn blocked JNKK2, c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated kinase 5, and AP-1 reporter gene activation by MEKK2. Furthermore, we found that the endogenous Mip1-MEKK2 complex was dissociated transiently following epidermal growth factor stimulation. In contrast, the knockdown of Mip1 expression by siRNA augmented the MEKK2-mediated JNK and AP-1 reporter activation. Together, our data suggest a novel model for MEKK2 regulation and activation.

* Corresponding author. Mailing address: Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030. Phone: (713) 563-3218. Fax: (713) 563-3357. E-mail: bsu{at}mdanderson.org.

Molecular and Cellular Biology, July 2005, p. 5955-5964, Vol. 25, No. 14
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.14.5955-5964.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ghosh, D., Srivastava, G. P., Xu, D., Schulz, L. C., Roberts, R. M. (2008). A link between SIN1 (MAPKAP1) and poly(rC) binding protein 2 (PCBP2) in counteracting environmental stress. Proc. Natl. Acad. Sci. USA 105: 11673-11678 [Abstract] [Full Text]  
  • Makino, C., Sano, Y., Shinagawa, T., Millar, J. B. A., Ishii, S. (2006). Sin1 binds to both ATF-2 and p38 and enhances ATF-2-dependent transcription in an SAPK signaling pathway. GENES CELLS 11: 1239-1251 [Abstract] [Full Text]  
  • Yang, Q., Inoki, K., Ikenoue, T., Guan, K.-L. (2006). Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity.. Genes Dev. 20: 2820-2832 [Abstract] [Full Text]  
  • Nakamura, K., Uhlik, M. T., Johnson, N. L., Hahn, K. M., Johnson, G. L. (2006). PB1 Domain-Dependent Signaling Complex Is Required for Extracellular Signal-Regulated Kinase 5 Activation.. Mol. Cell. Biol. 26: 2065-2079 [Abstract] [Full Text]  
  • Blonska, M., Shambharkar, P. B., Kobayashi, M., Zhang, D., Sakurai, H., Su, B., Lin, X. (2005). TAK1 Is Recruited to the Tumor Necrosis Factor-{alpha} (TNF-{alpha}) Receptor 1 Complex in a Receptor-interacting Protein (RIP)-dependent Manner and Cooperates with MEKK3 Leading to NF-{kappa}B Activation. J. Biol. Chem. 280: 43056-43063 [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»