Nucleic Acids Research, Vol 26, Issue 20 4771-4777, Copyright © 1998 by Oxford University Press
CC Yang, OI Ornatsky, JC McDermott, TF Cruz and CA Prody
Myocyte enhancer factor 2 (MEF2) has been implicated in the complex
hierarchical regulation of muscle-specific gene expression and
differentiation. While the MyoD family members are able to initiate the
skeletal muscle differentiation program, whether MEF2 is sufficient in
directing skeletal muscle differentiation is still controversial.
Furthermore, how MEF2 transactivates its target genes is not fully
understood. It has been suggested that the interactions of MEF2 with other
factors modify its transcriptional activity. Therefore, the identification
of MEF2-interacting factors may be important in understanding the mechanism
by which MEF2 activates its target genes. In this study, a
mitogen-activated protein kinase (MAP kinase), ERK5/BMK1 was found to
interact with MEF2 in a yeast two hybrid screen. The interaction was
confirmed by a glutathione S -transferase-pull down assay and a
co-immunoprecipitation study indicating that endogenous ERK5 and MEF2
interact with each other in vivo . The interacting domain of MEF2 was
mapped to the N-terminus which contains the highly conserved MADS and MEF2
domains. Functionally, ERK5/BMK1 was able to phosphorylate MEF2 in vitro .
Furthermore, when cotransfected with ERK5/BMK1, the transactivation
capacity of MEF2 was enhanced. These results suggest that the functions of
MEF2 could be regulated through ERK5/BMK1.
ARTICLES
Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen- activated protein kinase, ERK5/BMK1
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
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