High impact information on Mapkapk5

• However, relatively little is known about the signaling pathways mediating the senescence response. p38-regulated/activated protein kinase (PRAK) is a p38 MAPK substrate whose physiological functions are poorly understood [1].
• In primary cells, inactivation of PRAK prevents senescence and promotes oncogenic transformation [1].
• Furthermore, we show that PRAK activates p53 by direct phosphorylation [1].
• There are currently 11 vertebrate MKs in five subfamilies based on primary sequence homology: the ribosomal S6 kinases, the mitogen- and stress-activated kinases, the MAPK-interacting kinases, MAPK-activated protein kinases 2 and 3, and MK5 [2].
• Endogenous MK5 activity is significantly reduced by siRNA-mediated knockdown of ERK3 and also in fibroblasts derived from ERK3-/- mice [3].

Biological context of Mapkapk5

• Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway [3].
• We conclude that the differences between the phenotypes of MK5- and MK2-deficient mice result from clearly different functional properties of both enzymes [4].
• To explain this discrepancy, we used wild-type cells and embryonic fibroblasts from both MK2 and MK5 knockout mice as controls to reexamine the mechanism of activation, the interaction with endogenous p38 MAPK, and the substrate specificity of both enzymes [4].
• In mouse embryonic development, mRNA expression patterns of ERK3 and MK5 suggest spatiotemporal coexpression of both kinases [5].
• Furthermore, we have shown that the C-terminal domain of MK5 contains both a functional nuclear localization signal (NLS) and a leucine-rich nuclear export signal (NES), indicating that the subcellular distribution of this kinase reflects the relative activities of these two signals [6].

Anatomical context of Mapkapk5

• Furthermore, increased levels of ERK3 protein detected during nerve growth factor-induced differentiation of PC12 cells are accompanied by an increase in MK5 activity [3].
• We demonstrate that the distribution of Hsp25 and MK5 in the epidermis at the beginning of stratification and before keratinization is similar to that observed in PAM212 keratinocytes [7].
• Analysis of urine function of PRAKP mice reveals an unexpected P-dependent proliferative activity of PR-B in the epithelium and provides evidence that the tissue-specific reproductive effects of this isoform are due to specificity of target gene transactivation rather than differences in tissue-specific expression relative to PR-A [8].

Associations of Mapkapk5 with chemical compounds

• In contrast to MK2, which shows interaction with and chaperoning properties for p38 MAPK and which is activated by extracellular stresses such as arsenite or sorbitol treatment, endogenous MK5 did not show these properties [4].
• Targets of p38 include transcription factors, components of the translational machinery, and downstream serine/threonine kinases, including MAPK-activated protein kinase 5 (MK5) [6].

Enzymatic interactions of Mapkapk5

• Furthermore, endogenous MK5 is not able to phosphorylate Hsp27 in vitro and in vivo [4].

Regulatory relationships of Mapkapk5

• In support of this, we have shown that stress-induced activation of the p38 MAPK stimulates the chromosomal region maintenance 1 protein-dependent nuclear export of MK5 [6].

References