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Mitogen-activated protein kinase kinase kinase kinase 4

MAP4K4, Nck-interacting kinase, HGK, mitogen-activated protein kinase kinase kinase kinase 4
The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: Nck, JNK, AP-1, TRAF2, TNIK
Papers on MAP4K4
Identification of Phosphorylation Consensus Sequences and Endogenous Neuronal Substrates of the Psychiatric Risk Kinase TNIK.
Ehlers et al., Worcester, United States. In J Pharmacol Exp Ther, Feb 2016
Traf2- and Nck-interacting kinase (TNIK) is a serine/threonine kinase highly expressed in the brain and enriched in the postsynaptic density of glutamatergic synapses in the mammalian brain.
Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells.
Liao et al., Shanghai, China. In Mol Med Report, Jan 2016
Previous studies suggest that mitogen‑activated protein kinase kinase kinase kinase isoform 4 (MAP4K4) is involved in cancer cell growth, apoptosis and migration.
A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells.
Zheng et al., Frederick, United States. In Nucleic Acids Res, Jan 2016
By global profiling of the SRSF3-regulated splicing events in human osteosarcoma U2OS cells, we found that SRSF3 regulates the expression of 60 genes including ERRFI1, ANXA1 and TGFB2, and 182 splicing events in 164 genes, including EP300, PUS3, CLINT1, PKP4, KIF23, CHK1, SMC2, CKLF, MAP4, MBNL1, MELK, DDX5, PABPC1, MAP4K4, Sp1 and SRSF1, which are primarily associated with cell proliferation or cell cycle.
microRNA-622 acts as a tumor suppressor in hepatocellular carcinoma.
Xu et al., Shanghai, China. In Cancer Biol Ther, Jan 2016
Bioinformatic analysis and luciferase reporter assays revealed that miR-622 directly targeted the 3'-untranslated region (UTR) of mitogen-activated protein 4 kinase 4 (MAP4K4) mRNA.
Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment.
Wang et al., Cambridge, United States. In Acs Med Chem Lett, Dec 2015
Recent studies in adipose tissue, pancreas, muscle, and macrophages suggest that MAP4K4, a serine/threonine protein kinase may be a viable target for antidiabetic drugs.
MAP4K4 regulates integrin-FERM binding to control endothelial cell motility.
Ye et al., San Francisco, United States. In Nature, Apr 2015
Consequently, loss of moesin (encoded by the MSN gene) or MAP4K4 reduced adhesion disassembly rate in endothelial cells.
MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway.
Guan et al., San Diego, United States. In Nat Commun, 2014
We have identified MAP4K family members--Drosophila Happyhour homologues MAP4K1/2/3 and Misshapen homologues MAP4K4/6/7-as direct LATS1/2-activating kinases.
MicroRNA-194 acts as a prognostic marker and inhibits proliferation in hepatocellular carcinoma by targeting MAP4K4.
Zhao et al., Xinxiang, China. In Int J Clin Exp Pathol, 2014
Mitogen-activated protein kinase 4 (MAP4K4), a potential target gene of miR-194, was inversely correlated with miR-194 expression in HCC tissues and cell lines.
Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer.
Sugihara et al., Tokyo, Japan. In Bmc Cancer, 2014
Thus, we identified seventeen candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways.
Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis.
Czech et al., Worcester, United States. In Nat Commun, 2014
Here we demonstrate that the Sterile-20-like mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), which has been implicated in inflammation, is abundantly expressed in ECs and in atherosclerotic plaques from mice and humans.
A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS.
Rubin et al., Cambridge, United States. In Cell Stem Cell, 2013
Among the hits we found, kenpaullone had a particularly impressive ability to prolong the healthy survival of both types of MNs that can be attributed to its dual inhibition of GSK-3 and HGK kinases.
MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic β-cells.
Tang et al., China. In J Biol Chem, 2012
MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic beta-cells.
TNF-α involvement in insulin resistance induced by experimental scorpion envenomation.
Laraba-Djebari et al., Algiers, Algeria. In Plos Negl Trop Dis, 2011
These findings suggest that scorpion venom induces insulin resistance by mechanisms involving TNF-alpha-dependent Map4k4 kinase activation in the adipose tissue.
Splenic extramedullary hemopoiesis caused by a dysfunctional mutation in the NF-κB-inducing kinase gene.
Akiyama et al., Tokyo, Japan. In Biochem Biophys Res Commun, 2011
These data together with previous reports on extramedullary hemopoiesis in RelB-deficient mice suggest that NIK-RelB signaling may be involved in the suppression of extramedullary hemopoiesis in adult mice.
Smad inhibition by the Ste20 kinase Misshapen.
Xu et al., Worcester, United States. In Proc Natl Acad Sci U S A, 2011
Targeted expression of an active form of Msn in the wing imaginal disk disrupted activation of endogenous MAD by Dpp and expression of the Dpp/MAD target gene.
ShRNA-targeted MAP4K4 inhibits hepatocellular carcinoma growth.
Zhang et al., Shanghai, China. In Clin Cancer Res, 2011
MAP4K4 overexpression is an independent predictor of poor prognosis of Hepatocellular Carcinoma patients, and inhibition of its expression might be of therapeutic significance
Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation.
Czech et al., Worcester, United States. In Nature, 2009
Screening with GeRPs for inflammation genes revealed that the mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) is a previously unknown mediator of cytokine expression.
ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation.
Hanash et al., New Orleans, United States. In Autoimmunity, 2008
In microarray experiments and real-time RT-PCR assays, we observed significant differences in RNA levels from ICF vs. control lymphoblasts for pro- and anti-apoptotic genes (BCL2L10, CASP1, and PTPN13); nitrous oxide, carbon monoxide, NF-kappaB, and TNFalpha signalling pathway genes (PRKCH, GUCY1A3, GUCY1B3, MAPK13; HMOX1, and MAP4K4); and transcription control genes (NR2F2 and SMARCA2).
RNAi screens reveal novel metabolic regulators: RIP140, MAP4k4 and the lipid droplet associated fat specific protein (FSP) 27.
Czech et al., Worcester, United States. In Acta Physiol (oxf), 2008
These short interfering RNA (siRNA)-based screens identified the transcriptional corepressor receptor interacting protein 140 (RIP140) (J Clin Invest 116: 125, 2006) and the mitogen-activated protein kinase (MAP4k4) (Proc Natl Acad Sci USA 103: 2087, 2006) as negative regulators of insulin-responsive hexose uptake and oxidative metabolism.
p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation.
Niswander et al., Aurora, United States. In Cell, 2006
Finally, p38 regulates E-cadherin protein expression downstream from NCK-interacting kinase (NIK) and independently of the regulation of transcription by Fibroblast Growth Factor (Fgf) signaling and Snail.
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