Visit our Expo - Redox and Inflammation signaling 2012

Session I : protein domains Poster I, 4
A novel Mitogen-Activated Protein Kinase docking site in the N terminus of MEK5alpha
organizes the components of the Extracellular Signal-Regulated Kinase 5 signaling
pathway
Jan Seyfried, Xin Wang, Giorgi Kharebava, and Cathy Tournier
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford
Road, Manchester M13 9PT, UK
The alternative splicing of the mek5 gene gives rise to two isoforms. MEK5beta lacks an
extended N terminus present in MEK5alpha. Comparison of their activities led us to identify a
novel mitogen-activated protein kinase (MAPK) docking site in the N terminus of MEK5 that
is distinct form the consensus motif identified in the other MAPK kinases. It consists of a
cluster of acidic residues at position 61 and positions 63-66. The formation of the
MEK5/extracellular signal-regulated kinase 5 (ERK5) complex is critical for MEK5 to
activate ERK5, to increase transcription via MEF2, and to enhance cellular survival in
response to osmotic stress. Certain mutations in the ERK5 docking site that prevent
MEK5/ERK5 interaction also abrogate the ability of MEKK2 to bind and activate MEK5.
However, the identification of MEK5 alpha mutants with selective binding defect
demonstrates that the MEK5/ERK5 interaction does not rely on the binding of MEK5a to
MEKK2 via their respective PB1 domains. Altogether these results establish that the N
terminus of MEK5a is critical for the specific organization of the components of the ERK5
signaling pathway.
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