Nuclear export of human p38 MAPK mediated by its substrate MAPKAPK2 or 3

Stable Identifier
R-HSA-450257
Type
Reaction [transition]
Species
Homo sapiens
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p38 MAPK alpha does not have a nuclear export signal (NES) and cannot leave the nucleus by itself, but rather needs to be associated with MAP kinase-activated protein kinase 2 (MAPKAPK2 or MK2). The NES of MAPKAPK2 facilitates the transport of both kinases from the nucleus to the cytoplasm but only after MK2 has been phosphorylated by p38alpha.

p38 MAPK alpha phosphorylates MK2 at Thr222, Ser272, and Thr334. The phosphorylation of Thr334 but not the kinase activity of MK2 has been demonstrated to be critical for the nuclear export of the p38 alpha - MK2 complex. Phosphorylation of Thr334 is believed to induce a conformational change in the complex exposing NES prior to interaction with the leptomycin B-sensitive nuclear export receptor.

Literature References
PubMed ID Title Journal Year
12171911 Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export

Meng, W, Swenson, LL, Fitzgibbon, MJ, Hayakawa, K, Ter Haar, E, Behrens, AE, Fulghum, JR, Lippke, JA

J Biol Chem 2002
9768359 Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2

Ben-Levy, R, Hooper, S, Wilson, R, Paterson, HF, Marshall, CJ

Curr Biol 1998
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