Disease relevance of Map2k5

• MEK5 induced a form of hypertrophy in which cardiomyocytes acquired an elongated morphology and sarcomeres were assembled in a serial manner [1].
• Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy [1].

High impact information on Map2k5

• Moreover, a dominant-negative MEK5 mutant specifically blocked LIF-induced elongation of cardiomyocytes and reduced expression of fetal cardiac genes without blocking other aspects of LIF-induced hypertrophy [1].
• The alternative splicing of the mek5 gene gives rise to two isoforms [2].
• Overall, this is the first study to rigorously establish the role of MEK5 in vivo as an activator of ERK5 and as an essential regulator of cell survival that is required for normal embryonic development [3].
• The absence of MEK5 does not affect cell cycle progression but sensitizes mouse embryonic fibroblasts (MEFs) to the ability of sorbitol to enhance caspase 3 activity [3].
• The phenotype of the mek5(-/-) embryos includes abnormal cardiac development as well as a marked decrease in proliferation and an increase in apoptosis in the heart, head, and dorsal regions of the mutant embryos [3].

Biological context of Map2k5

• Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway [3].
• Inhibition of ERK5, MEK5 activation or activation of MEKK2-deficient mast cells was associated with inhibition of MEF2C phosphorylation and a decrease in c-Jun expression [4].

Anatomical context of Map2k5

• Expression of the constitutively active MEK5 also increased the survival of BAF3 cells cultured in the absence of or in low concentrations of G-CSF [5].

Physical interactions of Map2k5

• Quiescent MEKK2 preferentially binds MEK5, and MEKK2 activation results in ERK5 activation [6].

Enzymatic interactions of Map2k5

• Activated MEK5 then phosphorylates and activates ERK5 [7].

Regulatory relationships of Map2k5

• The proliferation of BAF3 cells in response to G-CSF was inhibited by expression of a dominant-negative MEK5 but potentiated by expression of a constitutively active MEK5 [5].

Other interactions of Map2k5

• Of the two isoforms upstream of MAPK-kinase 5 (MEK5) known to exist, only the longer MEK5alpha isoform potently activates BMK1 [8].

Analytical, diagnostic and therapeutic context of Map2k5

• Furthermore, co-immunoprecipitation of MEKK2 and MEK5 from cell lysates shows that they form a complex in vivo [7].

References