The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Elk1  -  ELK1, member of ETS oncogene family

Mus musculus

Synonyms: ETS domain-containing protein Elk-1, Elk-1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Elk1

  • Elk1-deficient mice derived from Elk-1((137/0)) ES cells are viable and do not reveal strong phenotypical abnormalities, apart from male sterility [1].
  • In so doing, we provide evidence that the sterility of Elk1((137/0)) mice was not due to the absence of Elk-1 but rather the presence of HygTk [1].
  • The finding that the major adenovirus E1A and mitogen-activated protein kinase-phosphorylated Elk1 activation domains bind to Sur2 uniquely among the metazoan mediator subunits and the development of transcriptionally active nuclear extracts from WT and sur2-/- embryonic stem cells, reported here, allowed a direct test of the model [2].
  • Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli [3].
  • The delay before the onset of the long-term SRE binding was reduced when the crush was closer to the ganglion and was attributed to an Elk1 kinase that is activated by injury in the axon and retrogradely transported to the cell body [4].

Psychiatry related information on Elk1

  • Two sequence changes in DYX1C1, one involving the translation initiation sequence and an Elk-1 transcription factor binding site (-3G --> A) and a codon (1249G --> T), introducing a premature stop codon and truncating the predicted protein by 4 aa, associate alone and in combination with dyslexia [5].

High impact information on Elk1


Biological context of Elk1


Anatomical context of Elk1

  • The fibroblast complexes contain mainly Net-b followed by Sap1 and Elk1 [14].
  • To investigate physiological functions of Elk-1 in vivo, we generated Elk-1-deficient mice by homologous recombination in embryonic stem cells [11].
  • In contrast, down-regulation of endogenous Elk-1 in smooth muscle cells increased the expression of only telokin and SM22alpha, suggesting that smooth muscle-specific promoters are differentially sensitive to the inhibitory effects of Elk-1 [13].
  • However, involvement of the latter pathway was further assessed in nonsteroidogenic COS-1 cells transfected with the Elk1 trans-reporting plasmids and resulted in a significant increase in luciferase activity in response to mEGF [15].
  • In addition to its nuclear localization, Elk-1 is found throughout the cytoplasm, including localization in neuronal dendrites [Sgambato, V., Vanhoutte, P., Pages, C., Rogard, M., Hipskind, R., Besson, M. J. & Caboche, J. (1998) J. Neurosci. 18, 214-226], raising the possibility that Elk-1 may have alternative extranuclear functions in neurons [16].

Associations of Elk1 with chemical compounds

  • Moreover, administration of 17beta-estradiol or 4-estren-3alpha,17beta-diol to ovariectomized mice induces phosphorylation of ERKs, Elk-1, and C/EBPbeta, downregulates c-Jun, and upregulates the expression of egr-1, an ERK/SRE target gene [17].
  • Alanine scanning of the Elk-1 B-box reveals five predominantly hydrophobic residues which are essential for binding to SRF and for ternary complex formation in vitro and in vivo [18].
  • Consistent with this stimulation, GH rapidly and transiently stimulated the serine phosphorylation of Elk-1 [19].
  • Blockade of JNK protein kinase activity with SB 202190 prevented both Elk-1 transactivation and c-Fos induction [20].
  • Overexpression of C3G enhanced the Elk-1 activation synergistically with CrkL, while a C3G mutant lacking the guanine nucleotide exchange domain showed an inhibitory effect [21].

Physical interactions of Elk1


Enzymatic interactions of Elk1

  • We therefore investigated whether SAPKs similarly upregulate c-fos expression by phosphorylating Elk-1 [23].
  • In vitro kinase assays showed that hippocampal Erk-1/2 phosphorylates Elk-1 [24].

Regulatory relationships of Elk1


Other interactions of Elk1

  • However, Net differs from Elk1 and SAP1 in a number of ways [8].
  • We suggest that egr-1 activation by shear stress involves activation of Elk-1 but not c-jun activity [28].
  • Elk-1, a principal ternary complex factor and Ets domain-containing protein, is a substrate of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases [29].
  • Studies using a dominant negative Ha-Ras mutant demonstrated that the Elk-1 and ERK2 activation enhanced by CrkL and C3G was dependent on Ras [21].
  • The assay involves immobilization of the respective kinase substrates c-Jun, Elk1, or ATF2 on microtiter plates, addition of the kinase reaction mixture, and measurement of substrate phosphorylation using phospho-epitope-specific antibodies [30].

Analytical, diagnostic and therapeutic context of Elk1


  1. Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange. Cesari, F., Rennekampff, V., Vintersten, K., Vuong, L.G., Seibler, J., Bode, J., Wiebel, F.F., Nordheim, A. Genesis (2004) [Pubmed]
  2. Activation domain-mediator interactions promote transcription preinitiation complex assembly on promoter DNA. Cantin, G.T., Stevens, J.L., Berk, A.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  3. Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli. Fukuda, K., Tsuchihara, K., Hijikata, M., Nishiguchi, S., Kuroki, T., Shimotohno, K. Hepatology (2001) [Pubmed]
  4. Rapid electrical and delayed molecular signals regulate the serum response element after nerve injury: convergence of injury and learning signals. Lin, H., Bao, J., Sung, Y.J., Walters, E.T., Ambron, R.T., Ying, J.S. J. Neurobiol. (2003) [Pubmed]
  5. A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain. Taipale, M., Kaminen, N., Nopola-Hemmi, J., Haltia, T., Myllyluoma, B., Lyytinen, H., Muller, K., Kaaranen, M., Lindsberg, P.J., Hannula-Jouppi, K., Kere, J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Marais, R., Wynne, J., Treisman, R. Cell (1993) [Pubmed]
  7. Functional analysis of a growth factor-responsive transcription factor complex. Hill, C.S., Marais, R., John, S., Wynne, J., Dalton, S., Treisman, R. Cell (1993) [Pubmed]
  8. Net, a new ets transcription factor that is activated by Ras. Giovane, A., Pintzas, A., Maira, S.M., Sobieszczuk, P., Wasylyk, B. Genes Dev. (1994) [Pubmed]
  9. Grape seed extract inhibits EGF-induced and constitutively active mitogenic signaling but activates JNK in human prostate carcinoma DU145 cells: possible role in antiproliferation and apoptosis. Tyagi, A., Agarwal, R., Agarwal, C. Oncogene (2003) [Pubmed]
  10. Defective nuclear translocation of nuclear factor of activated T cells and extracellular signal-regulated kinase underlies deficient IL-2 gene expression in Wiskott-Aldrich syndrome. Cianferoni, A., Massaad, M., Feske, S., de la Fuente, M.A., Gallego, L., Ramesh, N., Geha, R.S. J. Allergy Clin. Immunol. (2005) [Pubmed]
  11. Mice deficient for the ets transcription factor elk-1 show normal immune responses and mildly impaired neuronal gene activation. Cesari, F., Brecht, S., Vintersten, K., Vuong, L.G., Hofmann, M., Klingel, K., Schnorr, J.J., Arsenian, S., Schild, H., Herdegen, T., Wiebel, F.F., Nordheim, A. Mol. Cell. Biol. (2004) [Pubmed]
  12. Net-targeted mutant mice develop a vascular phenotype and up-regulate egr-1. Ayadi, A., Zheng, H., Sobieszczuk, P., Buchwalter, G., Moerman, P., Alitalo, K., Wasylyk, B. EMBO J. (2001) [Pubmed]
  13. Smooth muscle-specific genes are differentially sensitive to inhibition by Elk-1. Zhou, J., Hu, G., Herring, B.P. Mol. Cell. Biol. (2005) [Pubmed]
  14. Net-b, a Ras-insensitive factor that forms ternary complexes with serum response factor on the serum response element of the fos promoter. Giovane, A., Sobieszczuk, P., Ayadi, A., Maira, S.M., Wasylyk, B. Mol. Cell. Biol. (1997) [Pubmed]
  15. Mechanisms of epidermal growth factor signaling: regulation of steroid biosynthesis and the steroidogenic acute regulatory protein in mouse Leydig tumor cells. Manna, P.R., Huhtaniemi, I.T., Wang, X.J., Eubank, D.W., Stocco, D.M. Biol. Reprod. (2002) [Pubmed]
  16. Elk-1 associates with the mitochondrial permeability transition pore complex in neurons. Barrett, L.E., Van Bockstaele, E.J., Sul, J.Y., Takano, H., Haydon, P.G., Eberwine, J.H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids. Kousteni, S., Han, L., Chen, J.R., Almeida, M., Plotkin, L.I., Bellido, T., Manolagas, S.C. J. Clin. Invest. (2003) [Pubmed]
  18. Molecular characterization of the B-box protein-protein interaction motif of the ETS-domain transcription factor Elk-1. Ling, Y., Lakey, J.H., Roberts, C.E., Sharrocks, A.D. EMBO J. (1997) [Pubmed]
  19. Growth hormone regulates ternary complex factors and serum response factor associated with the c-fos serum response element. Liao, J., Hodge, C., Meyer, D., Ho, P.S., Rosenspire, K., Schwartz, J. J. Biol. Chem. (1997) [Pubmed]
  20. CD28 signaling augments Elk-1-dependent transcription at the c-fos gene during antigen stimulation. Li, W., Whaley, C.D., Bonnevier, J.L., Mondino, A., Martin, M.E., Aagaard-Tillery, K.M., Mueller, D.L. J. Immunol. (2001) [Pubmed]
  21. CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3. Nosaka, Y., Arai, A., Miyasaka, N., Miura, O. J. Biol. Chem. (1999) [Pubmed]
  22. CSF-1 induces fos gene transcription and activates the transcription factor Elk-1 in mature osteoclasts. Yao, G.Q., Itokawa, T., Paliwal, I., Insogna, K. Calcif. Tissue Int. (2005) [Pubmed]
  23. Activation of ternary complex factor Elk-1 by stress-activated protein kinases. Gille, H., Strahl, T., Shaw, P.E. Curr. Biol. (1995) [Pubmed]
  24. Phosphorylation of hippocampal Erk-1/2, Elk-1, and p90-Rsk-1 during contextual fear conditioning: interactions between Erk-1/2 and Elk-1. Sananbenesi, F., Fischer, A., Schrick, C., Spiess, J., Radulovic, J. Mol. Cell. Neurosci. (2002) [Pubmed]
  25. Growth hormone stimulates phosphorylation and activation of elk-1 and expression of c-fos, egr-1, and junB through activation of extracellular signal-regulated kinases 1 and 2. Hodge, C., Liao, J., Stofega, M., Guan, K., Carter-Su, C., Schwartz, J. J. Biol. Chem. (1998) [Pubmed]
  26. Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein. Lim, J.Y., Kim, H., Jeun, S.S., Kang, S.G., Lee, K.J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  27. Inhibition of 12-O-tetradecanoylphorbol-13-acetate induction of c-fos mRNA by the protein kinase A inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide. Huang, Y.T., Lin, J.K., Lee, M.T. Biochem. Pharmacol. (1999) [Pubmed]
  28. Fluid shear stress activation of egr-1 transcription in cultured human endothelial and epithelial cells is mediated via the extracellular signal-related kinase 1/2 mitogen-activated protein kinase pathway. Schwachtgen, J.L., Houston, P., Campbell, C., Sukhatme, V., Braddock, M. J. Clin. Invest. (1998) [Pubmed]
  29. Urea-inducible Egr-1 transcription in renal inner medullary collecting duct (mIMCD3) cells is mediated by extracellular signal-regulated kinase activation. Cohen, D.M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  30. Enzyme-linked immunosorbent assay for measurement of JNK, ERK, and p38 kinase activities. Forrer, P., Tamaskovic, R., Jaussi, R. Biol. Chem. (1998) [Pubmed]
  31. C/EBP beta and Elk-1 synergistically transactivate the c-fos serum response element. Hanlon, M., Bundy, L.M., Sealy, L. BMC Cell Biol. (2000) [Pubmed]
  32. Transcriptional regulation of the cytosolic chaperonin theta subunit gene, Cctq, by Ets domain transcription factors Elk-1, Sap-1a, and Net in the absence of serum response factor. Yamazaki, Y., Kubota, H., Nozaki, M., Nagata, K. J. Biol. Chem. (2003) [Pubmed]
  33. Induction-independent recruitment of CREB-binding protein to the c-fos serum response element through interactions between the bromodomain and Elk-1. Nissen, L.J., Gelly, J.C., Hipskind, R.A. J. Biol. Chem. (2001) [Pubmed]
  34. Long-term depression activates transcription of immediate early transcription factor genes: involvement of serum response factor/Elk-1. Lindecke, A., Korte, M., Zagrebelsky, M., Horejschi, V., Elvers, M., Widera, D., Prüllage, M., Pfeiffer, J., Kaltschmidt, B., Kaltschmidt, C. Eur. J. Neurosci. (2006) [Pubmed]
WikiGenes - Universities