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Mitogen-activated protein kinase kinase kinase 11

MLK3, RhoE, mixed lineage kinase 3, Rnd3
The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: JNK, AP-1, Rhodopsin, CAN, V1a
Papers using MLK3 antibodies
Collagen I–mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1
Johnson Keith R. et al., In The Journal of Cell Biology, 2002
... Anti-DDR1 rabbit pAb (C-20), anti-Rap1 rabbit pAb, and anti-MLK3 rabbit pAb were obtained from Santa Cruz Biotechnology, Inc ...
Papers on MLK3
Rnd3/RhoE Modulates Hypoxia-Inducible Factor 1α/Vascular Endothelial Growth Factor Signaling by Stabilizing Hypoxia-Inducible Factor 1α and Regulates Responsive Cardiac Angiogenesis.
Chang et al., Wuhan, China. In Hypertension, Feb 2016
In this study, we identified Rnd3, a small Rho GTPase, as a proangiogenic factor participating in the regulation of the HIF1α-VEGF signaling cascade.
Chaperone-mediated autophagy regulates proliferation by targeting RND3 in gastric cancer.
Fan et al., Xi'an, China. In Autophagy, Feb 2016
Unsurprisingly, LAMP2A knockdown in gastric cancer (GC) cells hindered proliferation, accompanied with altered expression of cell cycle-related proteins and accumulation of RND3/RhoE.
Melanoma-expressed CD70 is involved in invasion and metastasis.
Tilkin-Mariamé et al., Toulouse, France. In Br J Cancer, Feb 2016
Increasing the levels of the trimeric form of CD70 through monoclonal antibody binding led to an increase in CD70+ melanoma cell invasiveness through MAPK pathway activation, RhoE overexpression, ROCK1 and MYPT1 phosphorylation decrease, and stress fibres and focal adhesions disappearance.
Esophageal Cancer Epigenomics and Integrome Analysis of Genome-Wide Methylation and Expression in High Risk Northeast Indian Population.
Saxena et al., New Delhi, India. In Omics, Nov 2015
These included four genes (PTK2, RND1, RND3, and UBL3) with promoter hypermethylation and downregulation, and 19 genes (SEMG2, CD97, CTNND2, CADM3, OMD, NEFM, FBN2, CTNNB1, DLX6, UGT2B4, CCDC80, PZP, SERPINA4, TNFSF13B, NPC1, COL1A1, TAC3, BMP8A, and IL22RA2) with promoter hypomethylation and upregulation.
Feedback regulation through myosin II confers robustness on RhoA signalling at E-cadherin junctions.
Yap et al., Brisbane, Australia. In Nat Cell Biol, Oct 2015
ROCK1 protects junctional RhoA by phosphorylating Rnd3 to prevent the cortical recruitment of the Rho suppressor, p190B RhoGAP.
Mixed Lineage Kinase 3 Mediates Release of C-X-C Motif Ligand 10-Bearing Chemotactic Extracellular Vesicles from Lipotoxic Hepatocytes.
Gores et al., San Diego, United States. In Hepatology, Oct 2015
BACKGROUND AND AIMS: Mixed lineage kinase 3 (MLK3) deficiency reduces macrophage associated-inflammation in a murine model of nonalcoholic steatohepatitis (NASH).
Pathophysiological Functions of Rnd3/RhoE.
Chang et al., Zhanjiang, China. In Compr Physiol, 2014
Rnd3, also known as RhoE, belongs to the Rnd subclass of the Rho family of small guanosine triphosphate (GTP)-binding proteins.
14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins.
Ridley et al., London, United Kingdom. In Cell, 2013
Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site.
Involvement of mixed lineage kinase 3 in cancer.
Chadee, Toledo, United States. In Can J Physiol Pharmacol, 2013
The MAP3K mixed lineage kinase 3 (MLK3) phosphorylates MAP2Ks to activate multiple MAPK signaling pathways, and MLK3 also has functions in cell signaling that are independent of its kinase activity.
Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells.
Chadee et al., Toledo, United States. In Exp Cell Res, 2012
The findings establish MLK3 as an important regulator of MMP expression and invasion in ovarian cancer cells.
Neuronal polarization is impaired in mice lacking RhoE expression.
Guasch et al., Valencia, Spain. In J Neurochem, 2012
These findings support our previous report revealing the important role of RhoE in the normal development of the nervous system
Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function.
Rana et al., Maywood, United States. In Proc Natl Acad Sci U S A, 2012
These findings collectively suggest that the MLK3-Pin1 signaling cascade plays a critical role in regulating the cell cycle, centrosome numbers, and oncogenesis.
HBx activates FasL and mediates HepG2 cell apoptosis through MLK3-MKK7-JNKs signal module.
Zheng et al., Xuzhou, China. In World J Gastroenterol, 2012
Data show that HBx can induce HepG2 cell apoptosis via a novel active MLK3-MKK7-JNKs signaling module to upregulate FasL protein expression.
Rnd1 and Rnd3 targeting to lipid raft is required for p190 RhoGAP activation.
Negishi et al., Kyoto, Japan. In Mol Biol Cell, 2012
role of the N-terminal region in signaling; Rnd1 and Rnd3 have a KERRA (Lys-Glu-Arg-Arg-Ala) sequence of amino acids in their N-terminus, which functions as the lipid raft-targeting determinant; the sequence mediates lipid raft targeting of p190 RhoGAP correlated with its activation
Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6.
Sahai et al., London, United Kingdom. In Nat Cell Biol, 2011
The DDR1-Par3/Par6 complex controls the localization of RhoE to cell-cell contacts, where it antagonizes ROCK-driven actomyosin contractility.
Rebuilding synaptic architecture in HIV-1 associated neurocognitive disease: a therapeutic strategy based on modulation of mixed lineage kinase.
Gendelman et al., Rochester, United States. In Neurotherapeutics, 2010
Work from our laboratories has validated mixed lineage kinase type 3 (MLK3) as an enzyme pathologically activated in the CNS by human immunodeficiency virus 1 (HIV-1) neurotoxins.
Novel cell death signaling pathways in neurotoxicity models of dopaminergic degeneration: relevance to oxidative stress and neuroinflammation in Parkinson's disease.
Rana et al., Ames, United States. In Neurotoxicology, 2010
Dr. Ajay Rana presented his recent work on the role of mixed lineage kinase-3 (MLK3) in neuroinflammatory processes in neurotoxic cell death.
KRAS signaling pathway alterations in microsatellite unstable gastrointestinal cancers.
Seruca et al., Porto, Portugal. In Adv Cancer Res, 2009
This review is focused on the molecular profile of alterations in members of the KRAS signaling pathway (EGFR, KRAS, BRAF, PIK3CA, RASSF1A, and MLK3 genes) in MSI gastrointestinal carcinomas.
PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE.
Sahai et al., London, United Kingdom. In Nat Cell Biol, 2008
PDK1 competes directly with RhoE for binding to ROCK1. In the absence of PDK1, negative regulation by RhoE predominates, causing reduced acto-myosin contractility and motility.
Function and regulation of Rnd proteins.
Chardin, Antibes, France. In Nat Rev Mol Cell Biol, 2006
Recent evidence has shown that Rnd3 (RhoE) is also involved in the regulation of cell-cycle progression and transformation, indicating that these proteins might have other, as yet unexplored roles.
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