MAP2K4

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.
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Gene name Gene Conserved 8-mer 7-mer symbol sites Chemokine Z (C-X-C motif) CXC 12 1 1 ligand 12 NOTCH-regulated ankyrin NRARP 1 1 repeat protein Astrotactin-1 ASTN1 1 1 Nasal embryonic LHRH NELF 1 1 factor K(Lysine) acetyl KAT6B 1 1 transferase 6B Protein kinase C, alpha PRKCA 1 1 EF-hand domain family, EFHD2 1 1 member D2 Mitogen-activated protein MAP2K4 1 1 kinase kinase 4 Zinc finger protein 219 ZNF219 1 1 Ring finger protein 165 RNF165 1 1 Protocadherin 7 PCDH7 1 1 EPH receptor A3 EPHA3 1 1 Insulin receptor IRS1 1 1 substrate 1 POU class 2 homeobox 1 POU2F1 1 1
Genes included in cluster 4 and 13 were related to cell cycle and renewal of stem cells (CCNB1, CCNA2, FGF7, MAP2K4, WNT5A, KITGL, and FGF5).
Griffin et al., "Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%," Cancer Research, vol.
Some of these low-frequency mutations were found in important cancer genes such as mitogen-activated protein kinase 4 (MAP2K4), discoidin domain receptor tyrosine kinase 2 (DDR2), and lysine (K)-specific methyltransferase 2D (KMT2D, also known as MLL2) (see online Supplemental Fig.
Meanwhile, MAPK signaling pathway molecules including MEKK1, ASK1 (MAP3K5), MLK2 (MAP3K10), MLK3, NIK, MEK1 (MAP2K1), MEK2 (MAP2K2), MEK4 (MAP2K4), MEK7 (MAP2K7), ERK1 (MAPK3), JNK1 (MAPK8) and JNK2 (MAPK9) were significantly up-regulated and revealed 2.00-4.09 fold increases in expression level (Table 1).
SVMicrO-based Expression Gene prediction correlation Final symbol score Score P value Score P value FOXP1 1.066 0.0043 0.508 0.016 1212 VEZF1 0.942 0.0060 0.4868 0.020 1179 NOVA1 0.896 0.0067 0.479 0.023 1160 CPEB3 0.858 0.0074 0.484 0.022 1149 MAP2K4 0.919 0.0064 0.322 0.097 1139 FAM120A 0.885 0.0069 0.341 0.082 1130 PCDHA3 0.983 0.0054 0.170 0.215 1125 SIRT1 0.927 0.0062 0.230 0.162 1117 PCDHA5 0.983 0.0054 0.148 0.233 1113 PTEN 0.898 0.0067 0.221 0.168 1104 PCDHA1 0.983 0.0054 0.140 0.239 1103 NBEA 0.752 0.0098 0.491 0.020 1102 ZFHX4 0.970 0.0056 0.154 0.229 1097 GLCE 0.798 0.0087 0.3231 0.096 1096 MAGI2 0.777 0.0092 0.321 0.097 1086 SATB2 0.801 0.0086 0.243 0.151 1078 LEF1 0.753 0.0098 0.291 0.112 1065 ATPBD4 0.819 0.0082 0.170 0.215 1060
In contrast, mutations in MAP3K1 and its "sister" gene MAP2K4 occurred in about 16 percent of patients and were linked to a good response to aromatase inhibitors.
Wang, "MicroRNA-802 plays a tumour suppressive role in tongue squamous cell carcinoma through directly targeting MAP2K4," Cell Proliferation, vol.
Many genes, such as serpins, BCL-2 proteins; tumor necrosis factor receptor superfamily, member 11a (TNFRSF11A), unc-13 homolog D (UNC13D), sphingosine, ArfGAP with FG repeats 1 (AGFG1), mitogen-activated protein kinase kinase 4 (MAP2K4), IGFBP7; receptor (TNFRSF)-interacting serine-threonine kinase 1 (R1PK1), were identified.
Three apoptosis-associated genes [apoptotic peptidase activating factor 1 (APAF1), [4] mitogen-activated protein kinase kinase 4 (MAP2K4), and tumor protein p53 (TP53)] involved in the p53-dependent apoptosis pathway were upregulated in PBMCs from RPs.
Term Count P value Genes MAPK signaling pathway 13 0.0062 RPS6KA5, AKT1, MAP4K4, MAP3K5, PLA2G4A, DUSP2, FGF9, TGFBR1, MAP2K4, MKNK2, PPP3R1, FGF12, DUSP6 Endocytosis 10 0.010 IGF1R, ADRB3, FLT1, TGFBR1, PSD3, VPS4B, DNAJC6, PSD2, ARAP2, LDLRAP1 Axon guidance 7 0.042 EPHA5, SEMA6A, PLXNA1, PPP3R1, SEMA4C, L1CAM, SRGAP1 Insulin signaling 6 0.0076 AKT1, L1CAM, IGF1R, IRS2, pathway SOCS7, RHOQ Focal adhesion 4 0.021 VCAM1, L1CAM, ITGA4, CERCAM Table 2: Small molecules which might reverse the dysregulation of AD in EC and HIP regions.