This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.00125-07v1 27/12/4566    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 Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakamura, K. Articles by Johnson, G. L. Search for Related Content PubMed PubMed Citation Articles by Nakamura, K. Articles by Johnson, G. L.

Noncanonical Function of MEKK2 and MEK5 PB1 Domains for Coordinated Extracellular Signal-Regulated Kinase 5 and c-Jun N-Terminal Kinase Signaling

Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7365

Received 19 January 2007/ Returned for modification 14 March 2007/ Accepted 9 April 2007

MEKK2 and MEK5 encode Phox/Bem1p (PB1) domains that heterodimerize with one another. MEKK2, MEK5, and extracellular signal-related kinase 5 (ERK5) form a ternary complex through interactions involving the MEKK2 and MEK5 PB1 domains and a 34-amino-acid C-terminal extension of the MEK5 PB1 domain. This C-terminal extension encodes an ERK5 docking site required for MEK5 activation of ERK5. The PB1 domains bind in a front-to-back arrangement, with a cluster of basic amino acids in the front of the MEKK2 PB1 domain binding to the back-end acidic clusters of the MEK5 PB1 domain. The C-terminal moiety, including the acidic cluster of the MEKK2 PB1 domain, is not required for MEK5 binding and binds MKK7. Quiescent MEKK2 preferentially binds MEK5, and MEKK2 activation results in ERK5 activation. Activated MEKK2 binds and activates MKK7, leading to JNK activation. The findings define how the MEKK2 and MEK5 PB1 domains are uniquely used for differential binding of two mitogen-activated protein kinase kinases, MEK5 and MKK7, for the coordinated control of ERK5 and c-Jun N-terminal kinase activation.

Published ahead of print on 23 April 2007.

This article has been cited by other articles:

• Nakamura, K., Zawistowski, J. S., Hughes, M. A., Sexton, J. Z., Yeh, L.-A., Johnson, G. L., Scott, J. E. (2008). Homogeneous Time-Resolved Fluorescence Resonance Energy Transfer Assay for Measurement of Phox/Bem1p (PB1) Domain Heterodimerization. J Biomol Screen 13: 396-405 [Abstract]  
• Sumimoto, H., Kamakura, S., Ito, T. (2007). Structure and Function of the PB1 Domain, a Protein Interaction Module Conserved in Animals, Fungi, Amoebas, and Plants. Sci Signal 2007: re6-re6 [Abstract] [Full Text]