Premium
Scaffolding by ERK3 regulates MK5 in development
Author(s) -
Schumacher Stefanie,
Laaß Kathrin,
Kant Shashi,
Shi Yu,
Visel Axel,
Gruber Achim D,
Kotlyarov Alexey,
Gaestel Matthias
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600467
Subject(s) - biology , kinase , autophosphorylation , microbiology and biotechnology , phosphorylation , protein kinase a , scaffold protein , signal transduction
Extracellular‐regulated kinase 3 (ERK3, MAPK6) is an atypical member of the ERKs, lacking the threonine and tyrosine residues in the activation loop, carrying a unique C‐terminal extension and being mainly regulated by its own protein stability and/or by autophosphorylation. Here we show that ERK3 specifically interacts with the MAPK‐activated protein kinase 5 (MK5 or PRAK) in vitro and in vivo . Expression of ERK3 in mammalian cells leads to nuclear‐cytoplasmic translocation and activation of MK5 and to phosphorylation of both ERK3 and MK5. Remarkably, activation of MK5 is independent of ERK3 enzymatic activity, but depends on its own catalytic activity as well as on a region in the C‐terminal extension of ERK3. In mouse embryonic development, mRNA expression patterns of ERK3 and MK5 suggest spatiotemporal coexpression of both kinases. Deletion of MK5 leads to strong reduction of ERK3 protein levels and embryonic lethality at about stage E11, where ERK3 expression in wild‐type mice is maximum, indicating a role of this signalling module in development.