MAP2K4

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MAP2K4

A gene on chromosome 17q11.2 that encodes a MAPK kinase belonging to a protein kinase signal transduction cascade. MAP2K4 is a dual-specificity kinase and an essential component of the MAP kinase signal transduction pathway. It is also an essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway, which is involved in the mitochondrial death signalling pathway, including the release cytochrome c, leading to apoptosis. With MAP2K7/MKK7, it is the only known kinase to directly activate the SAP/JNKs MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3; whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 also activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. It is widely expressed in tissues, especially in skeletal muscle.
References in periodicals archive ?
Plasma Derivacion Las proteinas VEGFR-2, (67) con O-hi- MMP-1, MKK4 y la proteina droxilamina/ del complemento C5 se RPC-MS/MS/LC- encuentran carboniladas en MS/MS personas obesas, lo que indica la existencia de procesos relacionados con estres oxidante.
Isoangustone A, a novel licorice compound, inhibits cell proliferation by targeting PI3K, MKK4, and MKK7 in human melanoma.
Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis.
The MAPKKK in JNK pathway includes MEKK1, MEKK2, MEKK3, and MEKK4, MLK, and ASK1 and MAPKK contain MKK4, MKK3, MKK6, and MKK7 [62, 63].
However, gene expression levels of two other metastasis suppressors, KISS1 and MKK4, were increased by ethanol.
4-10) The MKK4 and MKK7 MAPKKs have been shown to activate JNK, and the MKK3 and MKK6 MAPKKs serve as the major activators of the p38 MAPK.
Zhiqing Huang et al showed, about Real-time quantitative PCR, that the level of MKK4 expression was efficiently reduced by MKK4-specific siRNA.
Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene.
In the neurons, the MLK family of kinases serves as the major MAPKKS and phosphorylates MKK4 & MKK7, which in turn phosphorylate the JNKS.
However, several molecules, including TAK1/TAB1, are capable of activating the MAPKKs, MKK3/6 and MKK4, which in turn activate p38 and JNK, respectively (21).
3,19,20) This phosphorylation is regulated by upstream dual-specificity kinases (MAPK kinases, [MAPKKs]) including MKK3, MKK4, and MKK6, which are capable of phosphorylating MAPKs on both serine and threonine as well as on tyrosine residues.