Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation

Jinke Cheng, Dongyu Zhang, Kihwan Kim, Yingxin Zhao, Yingming Zhao, Bing Su

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5955-5964
Number of pages10
JournalMolecular and Cellular Biology
Volume25
Issue number14
DOIs
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

MAP Kinase Kinase Kinase 2
Dimerization
Mitogen-Activated Protein Kinases
Transcription Factor AP-1
Mitogen-Activated Protein Kinase 7
Mitogen-Activated Protein Kinase 8
MAP Kinase Kinase Kinases
Mitogen-Activated Protein Kinase Kinases
Eukaryotic Cells
Reporter Genes
Epidermal Growth Factor
Small Interfering RNA
Transcriptional Activation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation. / Cheng, Jinke; Zhang, Dongyu; Kim, Kihwan; Zhao, Yingxin; Zhao, Yingming; Su, Bing.

In: Molecular and Cellular Biology, Vol. 25, No. 14, 07.2005, p. 5955-5964.

Research output: Contribution to journalArticle

Cheng, Jinke ; Zhang, Dongyu ; Kim, Kihwan ; Zhao, Yingxin ; Zhao, Yingming ; Su, Bing. / Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 14. pp. 5955-5964.
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