Genomes and Genes
Gene Symbol: Elk1
Description: ELK1, member of ETS oncogene family
Alias: Elk-1, ETS domain-containing protein Elk-1
- Demir O, Korulu S, Yildiz A, Karabay A, Kurnaz I. Elk-1 interacts with neuronal microtubules and relocalizes to the nucleus upon phosphorylation. Mol Cell Neurosci. 2009;40:111-9 pubmed publisher..We propose that Elk-1 is anchored to neuronal microtubules in resting or unstimulated cells, and upon stimulation is phosphorylated, which relocalizes phospho-Elk-1 to the nucleus in neurons. ..
- Li X, Weng H, Xu C, Reece E, Yang P. Oxidative stress-induced JNK1/2 activation triggers proapoptotic signaling and apoptosis that leads to diabetic embryopathy. Diabetes. 2012;61:2084-92 pubmed publisher..Our results show that JNK1 and JNK2 are equally involved in diabetic embryopathy and that the oxidative stress-JNK1/2-caspase pathway mediates the proapoptotic signals and the teratogenicity of maternal diabetes...
- Wang W, Huang L, Huang Y, Yin J, Berk A, Friedman J, et al. Mediator MED23 links insulin signaling to the adipogenesis transcription cascade. Dev Cell. 2009;16:764-71 pubmed publisher..Here we show that the Med23 subunit of the Mediator Complex and its interacting transcription factor Elk1 are critical regulators of adipogenesis...
- Salvador J, Mittelstadt P, Belova G, Fornace A, Ashwell J. The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38 activation pathway. Nat Immunol. 2005;6:396-402 pubmed..Thus, constitutive activation of T cell p38 through the alternative pathway is prevented by Gadd45alpha, the absence of which results in p38 activation, T cell hyperproliferation and autoimmunity. ..
- Sharrocks A. Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture. Biochem Soc Trans. 2002;30:1-9 pubmed
- Godeny M, Sayeski P. ERK1/2 regulates ANG II-dependent cell proliferation via cytoplasmic activation of RSK2 and nuclear activation of elk1. Am J Physiol Cell Physiol. 2006;291:C1308-17 pubmed..ANG II-induced heterotrimeric G protein/PKCzeta activity resulted in a loss of ERK1/2 nuclear translocation, elk1 phosphorylation, and the remaining portion of c-fos transcriptional activity not dependent on c-Src/Yes/Fyn...
- Costello P, Nicolas R, Willoughby J, Wasylyk B, Nordheim A, Treisman R. Ternary complex factors SAP-1 and Elk-1, but not net, are functionally equivalent in thymocyte development. J Immunol. 2010;185:1082-92 pubmed publisher..Ectopic expression of Egr-1 restored positive selection in SAP-1 null thymocytes, establishing it (and possibly other Egr family members) as the major effector for ERK-SAP-1 signaling in thymocyte positive selection. ..
- Vanhoutte P, Nissen J, Brugg B, Gaspera B, Besson M, Hipskind R, et al. Opposing roles of Elk-1 and its brain-specific isoform, short Elk-1, in nerve growth factor-induced PC12 differentiation. J Biol Chem. 2001;276:5189-96 pubmed..This is blocked by mutating a normally cryptic nuclear export signal in Elk-1. These data provide new insights into molecular events underlying neuronal differentiation of PC12 cells mediated by the NGF-ERK signaling cascade. ..
- Bouschet T, Perez V, Fernandez C, Bockaert J, Eychene A, Journot L. Stimulation of the ERK pathway by GTP-loaded Rap1 requires the concomitant activation of Ras, protein kinase C, and protein kinase A in neuronal cells. J Biol Chem. 2003;278:4778-85 pubmed..Thus, this set of data indicated that GPCR-elicited GTP loading of Rap1 was not sufficient to stimulate efficiently ERK in PC12 cells and required the permissive co-stimulation of PKA, PKC, or Ras. ..
- Pearson H, Perez Mancera P, Dow L, Ryan A, Tennstedt P, Bogani D, et al. SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. J Clin Invest. 2011;121:4257-67 pubmed publisher..These data suggest that the polarity network could provide a new avenue for therapeutic intervention. ..
- Portier M, Combes T, Gully D, Maffrand J, Casellas P. Neurotensin type 1 receptor-mediated activation of krox24, c-fos and Elk-1: preventing effect of the neurotensin antagonists SR 48692 and SR 142948. FEBS Lett. 1998;432:88-93 pubmed
- Barrett L, van Bockstaele E, Sul J, Takano H, Haydon P, Eberwine J. Elk-1 associates with the mitochondrial permeability transition pore complex in neurons. Proc Natl Acad Sci U S A. 2006;103:5155-60 pubmed..These results show an association of the nuclear transcription factor Elk-1 with the mitochondrial PTP and suggest an additional extranuclear function for Elk-1 in neurons. ..
- Tamai Y, Taketo M, Nozaki M, Seldin M. Mouse Elk oncogene maps to chromosome X and a novel Elk oncogene (Elk3) maps to chromosome 10. Genomics. 1995;26:414-6 pubmedThe Elk protein is a member of the Ets family found in both vertebrates and invertebrates. Human ELK1 encoded by ELK1 binds alone or together with serum response factor to DNA and regulates gene expression in a variety of biological ..
- Zhou J, Hu G, Herring B. Smooth muscle-specific genes are differentially sensitive to inhibition by Elk-1. Mol Cell Biol. 2005;25:9874-85 pubmed
- Ingram D, Hiatt K, King A, Fisher L, Shivakumar R, Derstine C, et al. Hyperactivation of p21(ras) and the hematopoietic-specific Rho GTPase, Rac2, cooperate to alter the proliferation of neurofibromin-deficient mast cells in vivo and in vitro. J Exp Med. 2001;194:57-69 pubmed
- Rahim G, Araud T, Jaquier Gubler P, Curran J. Alternative splicing within the elk-1 5' untranslated region serves to modulate initiation events downstream of the highly conserved upstream open reading frame 2. Mol Cell Biol. 2012;32:1745-56 pubmed publisher..We present evidence that all these events are fine-tuned by the nature of the 5' UTR and the activity of the ? subunit of eukaryotic initiation factor 2 and provide insights into the neuronal specificity of sELK-1 expression. ..
- Ahmad N, Wang W, Nair R, Kapila S. Relaxin induces matrix-metalloproteinases-9 and -13 via RXFP1: induction of MMP-9 involves the PI3K, ERK, Akt and PKC-? pathways. Mol Cell Endocrinol. 2012;363:46-61 pubmed publisher..Our findings provide the first characterization of signaling cascade involved in the regulation of any MMP by relaxin and offer mechanistic insights on how relaxin likely mediates extracellular matrix turnover. ..
- Mayer S, Thiel G. Calcium influx into MIN6 insulinoma cells induces expression of Egr-1 involving extracellular signal-regulated protein kinase and the transcription factors Elk-1 and CREB. Eur J Cell Biol. 2009;88:19-33 pubmed publisher..The newly synthesized Egr-1 is biologically active and binds under physiological conditions to the genes encoding basic fibroblast growth factor, tumor necrosis factor alpha, transforming growth factor beta and PTEN. ..
- Hung C, Liu X, Kwon M, Kang Y, Chung S, Perrella M. Regulation of heme oxygenase-1 gene by peptidoglycan involves the interaction of Elk-1 and C/EBPalpha to increase expression. Am J Physiol Lung Cell Mol Physiol. 2010;298:L870-9 pubmed publisher..Moreover, silencing of C/EBPalpha in macrophages prevented induction of HO-1 promoter activity by either Elk-1 or PGN. These data provide further insight into the regulation and function of HO-1 by a mediator of Gram-positive bacteria. ..
- Mitra A, Gao L, Zucker I. Angiotensin II-induced upregulation of AT(1) receptor expression: sequential activation of NF-kappaB and Elk-1 in neurons. Am J Physiol Cell Physiol. 2010;299:C561-9 pubmed publisher..a cell neuronal model. These data imply a positive feedback mechanism that may impact neuronal discharge sensitivity in response to ANG II. ..
- Whitmarsh A, Shore P, Sharrocks A, Davis R. Integration of MAP kinase signal transduction pathways at the serum response element. Science. 1995;269:403-7 pubmed..The Elk-1 transcription factor therefore integrates MAP kinase signaling pathways in vivo to coordinate biological responses to different extracellular stimuli. ..
- Grevin D, Ung S, Denhez F, Dehem M, Quatannens B, Begue A, et al. Structure and organization of the mouse elk1 gene. Gene. 1996;174:185-8 pubmedIn the ets gene family of transcription factors, elk1 belongs to the subfamily of Ternary Complex Factors (TCFs) which bind to the Serum Response Element (SRE) in conjunction with a dimer of Serum Response Factors (SRFs)...
- Kim M, Park J, Choi E, Park H. Presenilin acts as a positive regulator of basal level activity of ERK through the Raf-MEK1 signaling pathway. Biochem Biophys Res Commun. 2005;332:609-13 pubmed..Furthermore, Elk-1 transcription activity also down-regulates in PS1(-/-) MEF cells. Collectively, our data suggest that PS can modulate the basal level of ERK activity through the Raf-MEK-dependent pathway. ..
- de Alvaro C, Nieto Vazquez I, Rojas J, Lorenzo M. Nuclear exclusion of forkhead box O and Elk1 and activation of nuclear factor-kappaB are required for C2C12-RasV12C40 myoblast differentiation. Endocrinology. 2008;149:793-801 pubmed..C2C12-RasV12C40 myoblasts cultured in low serum repressed phosphorylation of p44/p42MAPK and ELK1, resulting in cell cycle arrest and myogenic differentiation...
- Fletcher F, Renshaw B, Hollingsworth T, Baum P, Lyman S, Jenkins N, et al. Genomic organization and chromosomal localization of mouse Eplg2, a gene encoding a binding protein for the receptor tyrosine kinase elk. Genomics. 1994;24:127-32 pubmed..The first intron comprises approximately 8.5 kb of the entire 12-kb genomic sequence. Eplg2 was mapped to the mouse X chromosome by interspecific backcross analysis and is tightly linked to the androgen receptor (Ar) locus. ..
- Arbet Engels C, Janknecht R, Eckhart W. Role of focal adhesion kinase in MAP kinase activation by insulin-like growth factor-I or insulin. FEBS Lett. 1999;454:252-6 pubmed..Further analysis in FAK deficient fibroblasts suggested that FAK impedes MAP kinase activation by IGF-I or insulin. ..
- Tatler A, Habgood A, Porte J, John A, Stavrou A, Hodge E, et al. Reduced Ets Domain-containing Protein Elk1 Promotes Pulmonary Fibrosis via Increased Integrin Î±vÎ²6 Expression. J Biol Chem. 2016;291:9540-53 pubmed publisher..acting to markedly repress basal gene transcription, which responds to both the Ets domain-containing protein Elk1 (Elk1) and the glucocorticoid receptor (GR)...
- Zhong S, Fromm J, Johnson D. TBP is differentially regulated by c-Jun N-terminal kinase 1 (JNK1) and JNK2 through Elk-1, controlling c-Jun expression and cell proliferation. Mol Cell Biol. 2007;27:54-64 pubmed..These studies uncovered several new molecular events that distinguish the functions of JNK1 and JNK2 that are critical for their regulation of cellular proliferation. ..
- Rieder G, Tessier A, Qiao X, Madison B, Gumucio D, Merchant J. Helicobacter-induced intestinal metaplasia in the stomach correlates with Elk-1 and serum response factor induction of villin. J Biol Chem. 2005;280:4906-12 pubmed..Thus, H. pylori induction of villin in the stomach correlates with activation and cooperative binding of Elk-1 and the SRF to the proximal promoter of villin. ..
- Cesari F, Rennekampff V, Vintersten K, Vuong L, Seibler J, Bode J, et al. Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange. Genesis. 2004;38:87-92 pubmed..We previously generated an Elk-1 null allele (Elk1-137) in murine embryonic stem (ES) cells by homologous recombination...
- Hanlon M, Bundy L, Sealy L. C/EBP beta and Elk-1 synergistically transactivate the c-fos serum response element. BMC Cell Biol. 2000;1:2 pubmed..This suggests that SRF, TCF, and C/EBPbeta are all necessary for maximal induction of the c-fos SRE in response to mitogenic signaling by Ras. ..
- Gille H, Kortenjann M, Thomae O, Moomaw C, Slaughter C, Cobb M, et al. ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. EMBO J. 1995;14:951-62 pubmed..Our results indicate that phosphorylation regulates ternary complex formation by Elk-1, which is a prerequisite for the manifestation of its transactivation potential at the c-fos SRE. ..
- Wang S, Turner E. Expression of dopamine pathway genes in the midbrain is independent of known ETS transcription factor activity. J Neurosci. 2010;30:9224-7 pubmed publisher..These findings suggest that the ETS factors, while required for the generation of the DA phenotype in nematodes, do not play such a role in the mouse midbrain. ..
- Ge X, Chen C, Hui X, Wang Y, Lam K, Xu A. Fibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes. J Biol Chem. 2011;286:34533-41 pubmed publisher..The impairment in this signaling pathway may contribute to FGF21 resistance in obese mice. ..
- Patel M, Predescu D, Tandon R, Bardita C, Pogoriler J, Bhorade S, et al. A novel p38 mitogen-activated protein kinase/Elk-1 transcription factor-dependent molecular mechanism underlying abnormal endothelial cell proliferation in plexogenic pulmonary arterial hypertension. J Biol Chem. 2013;288:25701-16 pubmed publisher..Our findings identify a novel GrB-EH(ITSN)-dependent pathogenic p38(MAPK)/Elk-1 signaling pathway involved in the poorly understood process of PL formation in severe PAH. ..
- Buffet C, Catelli M, Hecale Perlemoine K, Bricaire L, García C, Gallet Dierick A, et al. Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor. PLoS ONE. 2015;10:e0145484 pubmed publisher..SRF and Elk-1 form a ternary complex (Elk-1-SRF-DNA) on DUSP5 promoter, consequently providing a link to an important negative feedback tightly regulating phosphorylated ERK levels. ..
- Giovane A, Sobieszczuk P, Mignon C, Mattei M, Wasylyk B. Locations of the ets subfamily members net, elk1, and sap1 (ELK3, ELK1, and ELK4) on three homologous regions of the mouse and human genomes. Genomics. 1995;29:769-72 pubmedNet, Elk1, and Sap1 are related members of the Ets oncoprotein family...
- Salmon M, Gomez D, GREENE E, Shankman L, Owens G. Cooperative binding of KLF4, pELK-1, and HDAC2 to a G/C repressor element in the SM22? promoter mediates transcriptional silencing during SMC phenotypic switching in vivo. Circ Res. 2012;111:685-96 pubmed publisher..The pELK-1-KLF4 complex in turn recruits HDAC2, leading to reduced histone acetylation and epigenetic silencing. ..
- Canbaz D, Kırımtay K, Karaca E, Karabay A. SPG4 gene promoter regulation via Elk1 transcription factor. J Neurochem. 2011;117:724-34 pubmed publisher..ETS (E Twenty Six-specific)-domain transcription factor, Elk1, has been shown to be important for synaptic plasticity and interact with microtubules...
- Wang G, Balamotis M, Stevens J, Yamaguchi Y, Handa H, Berk A. Mediator requirement for both recruitment and postrecruitment steps in transcription initiation. Mol Cell. 2005;17:683-94 pubmed..We show here that for the mouse Egr1 gene, controlled largely by MAP kinase phosphorylation of the ELK1 transcription factor, the MED23 Mediator subunit that interacts with phospho-ELK1 is also required to stimulate Pol ..
- Weinl C, Wasylyk C, Garcia Garrido M, Sothilingam V, Beck S, Riehle H, et al. Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae. PLoS ONE. 2014;9:e107048 pubmed publisher..of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown...
- Ying T, Hsieh Y, Hsieh Y, Liu J. Antisense oligonucleotide Elk-1 suppresses the tumorigenicity of human hepatocellular carcinoma cells. Cell Biol Int. 2008;32:210-6 pubmed..The maximum inhibitory rate of tumor growth was 80.8+/-12.6% and the tumor formation time was prolonged from 13 to 25 days. These findings suggested the usefulness of antisense ODN Elk-1 as a new reagent for liver cancer therapy. ..
- Bettelli E, Dastrange M, Oukka M. Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. Proc Natl Acad Sci U S A. 2005;102:5138-43 pubmed
- Kerr N, Pintzas A, Holmes F, Hobson S, Pope R, Wallace M, et al. The expression of ELK transcription factors in adult DRG: Novel isoforms, antisense transcripts and upregulation by nerve damage. Mol Cell Neurosci. 2010;44:165-77 pubmed publisher..We show by RT-PCR that the previously described Elk1, Elk3/Elk3b/Elk3c and Elk4 mRNAs are expressed in adult dorsal root ganglia (DRG), together with the novel ..
- Jiang J, Yang W, Huang P, Bu X, Zhang N, Li J. Increased phosphorylation of Ets-like transcription factor-1 in neurons of hypoxic preconditioned mice. Neurochem Res. 2009;34:1443-50 pubmed publisher..These results suggested that the enhanced neuron-specific phosphorylation of Elk-1 at Ser383 is involved in cerebral HPC of mice. ..
- Wuestefeld T, Pesic M, Rudalska R, Dauch D, Longerich T, Kang T, et al. A Direct in vivo RNAi screen identifies MKK4 as a key regulator of liver regeneration. Cell. 2013;153:389-401 pubmed publisher..Mechanistically, induction of MKK7 and a JNK1-dependent activation of the AP1 transcription factor ATF2 and the Ets factor ELK1 are crucial for increased regeneration of hepatocytes with MKK4 silencing.
- Meng F, Lowell C. A beta 1 integrin signaling pathway involving Src-family kinases, Cbl and PI-3 kinase is required for macrophage spreading and migration. EMBO J. 1998;17:4391-403 pubmed..These data provide a molecular description for the role of Src-family kinases Hck, Fgr and Lyn in beta 1-integrin signal transduction in macrophages. ..
- Al Sadi R, Guo S, Ye D, Ma T. TNF-? modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1. Am J Pathol. 2013;183:1871-1884 pubmed publisher..These studies provide novel insight into the cellular and molecular processes that regulate the TNF-?-induced increase in intestinal epithelial tight junction permeability. ..
- Qu K, Ma X, Li G, Zhang H, Liu Y, Zhang K, et al. Vitamin C down-regulate apo(a) expression via Tet2-dependent DNA demethylation in HepG2 cells. Int J Biol Macromol. 2017;98:637-645 pubmed publisher..Vitamin C can also increase ELK1 expression and hydroxymethylation of ELK1 promoter and the globle DNA in HepG2 cells...
- Lindecke A, Korte M, Zagrebelsky M, Horejschi V, Elvers M, Widera D, et al. Long-term depression activates transcription of immediate early transcription factor genes: involvement of serum response factor/Elk-1. Eur J Neurosci. 2006;24:555-63 pubmed..We suggest that LTD leads to SRF/Elk-1-regulated gene expression of immediate early transcription factors, which could in turn promote a second broader wave of gene expression. ..