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PMID:16973613

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Citation

Kant, S, Schumacher, S, Singh, MK, Kispert, A, Kotlyarov, A and Gaestel, M (2006) Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5. J. Biol. Chem. 281:35511-9

Abstract

The extracellular-regulated kinase (ERK) 4 (MAPK4) and ERK3 (MAPK6) are structurally related atypical MAPKs displaying major differences only in the C-terminal extension. ERK3 is known as an unstable mostly cytoplasmic protein that binds, translocates, and activates the MAPK-activated protein kinase (MK) 5. Here we have investigated the stability and expression of ERK4 and have analyzed its ability to bind, translocate, and activate MK5. We show that, in contrast to ERK3, ERK4 is a stable protein that binds to endogenous MK5. Interaction of ERK4 with MK5 leads to translocation of MK5 to the cytoplasm and to its activation by phosphorylation. In transfected HEK293 cells, where overexpressed catalytically dead ERK3 is able to activate MK5, catalytic activity of ERK4 is necessary for activation of MK5, indicating that ERK4 directly phosphorylates MK5. Interestingly, ERK4 dimerizes and/or oligomerizes with ERK3, suggesting that overexpressed inactive ERK3 recruits active endogenous ERK4 to MK5 for its activation. Hence, ERK3 and ERK4 cooperate in activation of MK5.

Links

PubMed Online version:10.1074/jbc.M606693200

Keywords

Cell Line; Enzyme Activation; Enzyme Stability; Gene Deletion; Humans; Intracellular Signaling Peptides and Proteins; Mitogen-Activated Protein Kinase 6/metabolism; Mitogen-Activated Protein Kinase Kinases/metabolism; Mutagenesis, Site-Directed; Protein Transport; Protein-Serine-Threonine Kinases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MAPK5

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MAPK5

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MAPK5

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MAPK5

enables

GO:0051019: mitogen-activated protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q6P5G0

F

Seeded From UniProt

complete

MOUSE:MK06

enables

GO:0046982: protein heterodimerization activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q6P5G0

F

Seeded From UniProt

complete

MOUSE:MK04

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MK04

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MK04

enables

GO:0042803: protein homodimerization activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MK04

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O54992

F

Seeded From UniProt

complete

MOUSE:MK04

enables

GO:0046982: protein heterodimerization activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61532

F

Seeded From UniProt

complete


See also

References

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