Signal uptake by the c-fos serum response element

  • Michael A. Cahill
  • Ralf Janknecht
  • Alfred Nordheim
Part of the Progress in Gene Expression book series (PRGE)


Detailed functional characterization of the c-fos serum response element (SRE) has identified this promoter segment as an important nuclear target structure for the uptake of mitogenic signals by the genome. The study of the SRE and its interacting proteins has permitted the retrograde connection with signaling steps activated upon stimulation of nonproliferating cells. The SRE is also targeted by nonmitogenic signaling events which similarly lead to the activation of c-fos. These include, e.g. heat treatment, neuronal stimulation, UV light, or reactive oxygen intermediates. Since SREs and SRE-like sequences are found in the promoters of many different genes, they may be crucial for the transmission of extra- and intracellular signals into responses at the level of gene activity.


Serum Response Factor Signal Uptake Serum Response Element Ternary Complex Formation MAPK Family Member 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alblas J, van Corven EJ, Hordijk PL, Milligan G, Moolenaar WH (1993): Gi-mediated activation of the p21ras-mitogen-activated protein kinase pathway by α2-adrenergic receptors expressed in fibroblasts. J Biol Chem 268: 22235–22238PubMedGoogle Scholar
  2. Almendral JM, Sommer D, MacDonald-Bravo H, Burckhardt J, Perera J, Bravo R (1988): Complexity of the early genetic response to growth factors in mouse fibroblasts. Mol Cell Biol 8: 2140–2148PubMedGoogle Scholar
  3. Amaya E, Musci TJ, Kirschner MW (1991): Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Cell 66: 257–270PubMedGoogle Scholar
  4. Ammerer G (1994): Sex, stress and integrity: importance of MAP kinases in yeast. Curr Opin Genet Dev 4: 90–95PubMedGoogle Scholar
  5. Aoyagi T, Izumo S (1993): Mapping of the pressure response element of the c-fos gene by direct DNA injection into beating hearts. J Biol Chem 268: 27176–27179PubMedGoogle Scholar
  6. Asaoka Y, Nakamura S-i, Yoshida K, Nishizuka Y (1992): Protein kinase C, calcium and phospholipid degradation. Trends Biochem Sci 17: 414–417PubMedGoogle Scholar
  7. Bading H, Ginty DD, Greenberg ME (1993): Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. Science 260:181–186PubMedGoogle Scholar
  8. Bergelson S, Pinkus R, Daniel V (1994): Induction of AP-1 (Fos/Jun) by chemical agents mediates activation of glutathione S-transferase and quinone reductase gene expression. Oncogene 9: 565–571PubMedGoogle Scholar
  9. Berra E, Diaz-Meco MT, Dominguez I, Municio MM, Sanz L, Lozano J, Chapkin RS, Moscat J (1993): Protein kinase C f isoform is critical for mitogenic transduction. Cell 74: 555–563PubMedGoogle Scholar
  10. Berridge MJ (1993): Inositol trisphosphate and calcium signalling. Nature 361: 351–325Google Scholar
  11. Bhattacharya G, Lee L, Reddy ESP, Rao VN (1993): Transcriptional activation domains of elk-1, Δelk-1 and SAP-1 proteins. Oncogene 8: 3459–3464PubMedGoogle Scholar
  12. Birge RB, Hanafusa H (1983): Closing in on SH2 specificity. Science 262: 1522–1524Google Scholar
  13. Blenis J (1993): Signal transduction via the MAP kinases: proceed at your own RSK. Proc Natl Acad Sci USA 90: 5889–5892PubMedGoogle Scholar
  14. Blum S, Forsdyke RE, Forsdyke DR (1990): Three human homologs of a murine gene encoding an inhibitor of stem cell proliferation. DNA Cell Biol 9: 589–602PubMedGoogle Scholar
  15. Boguski MS, McCormick F (1993): Proteins regulating Ras and its relatives. Nature 366: 643–654PubMedGoogle Scholar
  16. Bornstein P (1992): Thrombospondins: structure and regulation of expression. FASEB J 6: 3290–3299PubMedGoogle Scholar
  17. Borrelli E, Montamayeur J-P, Foulkes NS, Sassone-Corsi P (1992): Signal transduction and gene control: the cAMP pathway. Crit Rev Oncogen 3(4): 321–338Google Scholar
  18. Boulden A, Sealy L (1990): Identification of a third protein factor which binds to the Rous Sarcoma Virus LTR enhancer: possible homology with the serum response factor. Virol 174: 204–216Google Scholar
  19. Bravo R (1990): Genes induced during the G0/G1 transition in mouse fibroblasts. Cancer Biology 1: 37–46Google Scholar
  20. Brunner D, Oellers N, Szarbad J, Biggs WH III, Zipursky SL, Hafen E (1994): A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways. Cell 76: 875–888PubMedGoogle Scholar
  21. Büscher D, Sbarba PD, Hipskind RA, Rapp UR, Stanley ER, Baccarini M (1993): v-raf confers CSF-1 independent growth to a macrophage cell line and leads to immediate early gene expression without MAP-kinase activation. Oncogene 8: 3323–3332PubMedGoogle Scholar
  22. Cai H, Erhardt P, Troppmair J, Diaz-Meco MT, Sithanandam G, Rapp UR, Moscat J, Cooper GM (1993): Hydrolysis of phosphatidylcholine couples Ras to activation of Raf protein kinase during mitogenic signal transduction. Mol Cell Biol U: 7645–7651Google Scholar
  23. Carroll MP, Stratford M W (1994): Protein kinase C-mediated serine phosphorylation directly activates Raf-1 in murine hematopoietic cells. J Biol Chem 269: 1249–1256PubMedGoogle Scholar
  24. Chang Y-N, Jeang K-T, Chiou C-J, Chan Y-J, Pizzorno M, Hayward S (1993): Identification of a large bent DNA domain and binding sites for serum response factor adjacent to the NF1 repeat cluster and enhancer region in the major IE94 promoter from Simian Cytomegalovirus. J Virol 67: 516–529PubMedGoogle Scholar
  25. Charles CH, Abler AS, Lau LF (1992): cDNA sequence of a growth factor-inducible immediate early gene and characterization of its encoded protein. Oncogene 7: 187–190Google Scholar
  26. Charles CH, Simske, JS, O’Brien TP, Lau LF (1990): PiP92: a short-lived, growth factor-inducible protein in BALB/c 3T3 and PC12 cells. Mol Cell Biol 10: 6769–6774PubMedGoogle Scholar
  27. Chavrier P, Zerial M, Lemaire P, Almendral J, Bravo R, Charnay P (1988): A gene encoding a protein with zinc fingers is activated during G0/Gi transition in cultured cells. EMBO J 7: 29–36PubMedGoogle Scholar
  28. Chen R-H, Abate C, Blenis J (1993): Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDA ribosomal S6 kinase. Proc Natl Acad Sci USA 90: 10956–10956Google Scholar
  29. Christy B, Nathans D (1989): Functional serum response elements upstream of the growth factor inducible zif268. Mol Cell Biol 9: 4889–4895PubMedGoogle Scholar
  30. Coffer P, de Jonge M, Mettouchi A, Binetruy B, Ghysdael J, Kruijer W (1994): junB promoter regulation: Ras mediated transactivation by c-Ets-1 and c-Ets-2. Oncogene 9: 911–921Google Scholar
  31. Cohen DR, Curran T (1989): The structure and function of the fos proto-oncogene. Oncogenesis 1: 65–88Google Scholar
  32. Cohen P (1992): Signal integration at the level of protein kinases, protein phosphatases and their substrates. Trends Biochem Sci 17: 408–413PubMedGoogle Scholar
  33. Crews CM, Alessandrini A, Erikson RL (1992): The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. Science 258: 478–480PubMedGoogle Scholar
  34. Dalton S, Treisman R (1992): Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell 68: 597–612PubMedGoogle Scholar
  35. Davis RJ (1993): The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268: 14553–14556PubMedGoogle Scholar
  36. Dekker LV, Parker PJ (1994): Protein kinase C — a question of specificity. Trends Biochem Sci 19: 73–77PubMedGoogle Scholar
  37. Dérijard B, Hibi M, Wu I-H, Barret T, Su B, Deng T, Karin M, Davis RJ (1994): JNK1: A Protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76: 1–20Google Scholar
  38. Diaz-Benjumea F J, Hafen E (1994): The sevenless signalling cassette mediates Drosophila receptor function during epidermal development. Development 120: 569–578PubMedGoogle Scholar
  39. Erikson RL (1991): Structure, expression, and regulation of protein kinases involved in the phosphorylation of ribosomal protein S6. J Biol Chem 266: 6007–6010PubMedGoogle Scholar
  40. Ernst WH, Janknecht R, Cahill MA, Nordheim A (1994): Transcriptional activation and repression mediated by the serum response factor. Manuscript submittedGoogle Scholar
  41. Ettehadieh E, Sanghera JS, Pelech SL, Hess-Bienz D, Watts J, Shastri N, Aebersold R (1992): Tyrosyl phosphorylation and activation of MAP kinases by p56 lck . Science 255: 853–855PubMedGoogle Scholar
  42. Fantl WJ, Johnson DE, Williams LT (1993): Signalling by receptor tyrosine kinases. Annu Rev Biochem 62: 453–481PubMedGoogle Scholar
  43. Feig LA (1993): The many roads that lead to Ras. Science 260: 767–768PubMedGoogle Scholar
  44. Framson P, Bornstein P (1993): A serum response element and a binding site for NF-Y mediate the serum response of the human thrombospondin Z gene. J Biol Chem 268: 4989–4996PubMedGoogle Scholar
  45. Frödin M, Peraldi P, Van Obberghen E (1994): Cyclic AMP activates the mitogen-activated protein kinase cascade in PC12 cells. J Biol Chem 269: 6207–6214PubMedGoogle Scholar
  46. Fujii M, Tsuchiya H, Chuhjo T, Akizawa T, Seiki M (1992): Interaction of HTLV-1 Taxi with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes. Genes Dev 6: 2066–2076PubMedGoogle Scholar
  47. Gardner AM, Vaillancourt RR, Johnson GL (1993): Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase by G protein and tyrosine kinase oncoproteins. J Biol Chem 268: 17896–17901PubMedGoogle Scholar
  48. Gauthier-Rouvière C, Basset M, Blanchard J-M, Cavadore J-C, Fernandez A, Lamb NJC (1991): Casein kinase II induces c-fos expression via the serum response element pathway and p67SRF phosphorylation in living fibroblasts. EMBO J 10: 2921–2930PubMedGoogle Scholar
  49. Gille HG, Sharrocks AD, Shaw PE (1992): Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at the c-fos promoter. Nature 358: 414–417PubMedGoogle Scholar
  50. Gilman MZ, Wilson RN, Weinberg RA (1986): Multiple protein binding sites in the 5′ flanking region regulate c-fos expression. Mol Cell Biol 6: 4305–4314PubMedGoogle Scholar
  51. Greenberg ME, Ziff EB (1984): Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311: 433–438PubMedGoogle Scholar
  52. Grueneberg DA, Natesan S, Alexandre C, Gilman MZ (1992): Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor. Science 257: 1089–1095PubMedGoogle Scholar
  53. Gualberto A, LePage D, Pons G, Mader SL, Park K, Atchison ML, Walsh K (1992): Functional antagonism between YY1 and the serum response factor. Mol Cell Biol 12: 4209–4214PubMedGoogle Scholar
  54. Gutman A, Wasylyk C, Wasylyk B (1991): Cell-specific regulation of oncogene-responsive sequences of the c-fos promoter. Mol Cell Biol 11: 5381–5387PubMedGoogle Scholar
  55. Hata A, Akita Y, Suzuki K, Ohno S (1993): Functional divergence of protein kinase C (PKC) family members. J Biol Chem 268: 9122–9129PubMedGoogle Scholar
  56. Hayes TE, Kitchen AM, Cochran BH (1987): Inducible binding of a factor to the c-fos regulatory region. Proc Natl Acad Sci USA 84: 1217–1225Google Scholar
  57. Heidecker G, Kölch W, Morrison DK, Rapp UR (1992): The role of Raf-1 phosphorylation in signal transduction. Adv Cancer Res 58: 53–73PubMedGoogle Scholar
  58. Hepler JR, Gilman AG (1992): G proteins. Trends Biochem Sci 17: 383–387PubMedGoogle Scholar
  59. Herrera RE, Shaw PE, Nordheim A (1989): Occupation of the c-fos serum response element in vivo by a multi-protein complex is unaltered by growth factor induction. Nature 340: 68–70PubMedGoogle Scholar
  60. Hibi M, Lin A, Smeal T, Minden A, Karin M (1993): Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev 7: 2135–2148PubMedGoogle Scholar
  61. Hiles ID, Otsu M, Volinia S, Fry MJ, Gout I, Dhand R, Panayotou G, Ruiz-Larrea F, Thompson A, Totty NF, Hsuan JJ, Courtneidge SA, Parker PJ, Waterfield MD (1992): Phosphatidylinositol 3-kinase: structure and expression of 110kd catalytic subunit. Cell 70: 419–429PubMedGoogle Scholar
  62. Hill CS, Marais R, John S, Wynne J, Dalton S, Treisman R (1993): Functional analysis of a growth factor-responsive transcription factor complex. Cell 73: 395–406PubMedGoogle Scholar
  63. Hipskind RA, Nordheim A (1991): Functional dissection in vitro of the human c-fos promoter. J Biol Chem 266: 19583–19592PubMedGoogle Scholar
  64. Hipskind RA, Rao VN, Mueller CGF, Reddy ESP, Nordheim A (1991): Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Nature 354: 531–534PubMedGoogle Scholar
  65. Holt JT (1993): Antisense rescue defines specialized and generalized functional domains for c-Fos protein. Mol Cell Biol 13: 3821–3830PubMedGoogle Scholar
  66. Holt JT, Gopal TV, Moulton AD, Nienhuis AQ (1986): Inducible production of c-fos anti-sense RNA inhibits 3T3 cell proliferation. Proc Natl Acad USA 83:4794–4798Google Scholar
  67. Hordijk PL, Verlaan I, Jalink K, van Corven EJ, Moolenaar WH (1994a): cAMP abrogates the p21ras-mitogen activated protein kinase pathway in fibroblasts. J Biol Chem 269: 3534–3538PubMedGoogle Scholar
  68. Hordijk PL, Verlaan I, van Corven EJ, Moolenaar WH (1994b): Protein tyrosine phosphorylation induced by lysophosphatidic acid in Rat-1 fibroblasts. J Biol Chem 269: 645–651PubMedGoogle Scholar
  69. Howe LR, Marshall CJ (1993): Lysophosphatidic acid stimulates mitogen-activated protein kinase activation via a G-protein-coupled pathway requiring p21ras and p74raf-1. J Biol Chem 268: 20717–20720PubMedGoogle Scholar
  70. Hu P, Mondino A, Skolnik EY, Schlessinger J (1993): Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85. Moll Cell Biol 13: 7677–7688Google Scholar
  71. Hug H, Sarre TF (1993): Protein kinase C isoenzymes: divergence in signal transduction? Biochem J 291: 329–343PubMedGoogle Scholar
  72. Inglese J, Freedman NJ, Koch W J, Lefkowitz RJ (1993): Structure and mechanism of the G protein-coupled receptor kinases. J Biol Chem 268: 23735–23738PubMedGoogle Scholar
  73. Itoh T, Kaibuchi K, Masuda T, Yamamoto Y, Matsuura Y, Maeda A, Shimizu K, Takai Y (1993): A protein factor for ras p21-dependent activation of mitogen-activated protein (MAP) kinase through MAP kinase kinase. Proc Natl Acad Sci USA 90: 975–979PubMedGoogle Scholar
  74. Iyengar R (1993): Multiple families of GS-regulated adenylyl cyclases. Advances in Second Messenger and Phosphoprotein Research 28: 27–36PubMedGoogle Scholar
  75. Jaiswal RK, Murphy MB, Landreth GE (1993): Identification and characterization of a nerve growth factor-stimulated mitogen-activated protein kinase activator in PC12 cells. J Biol Chem 268: 7055–7063PubMedGoogle Scholar
  76. Jamal S, Ziff EB (1990): Transactivation of c-fos and β-actin genes by raf as a step in early response to transmembrane signals. Nature 344: 463–466PubMedGoogle Scholar
  77. Janknecht R, Nordheim A (1992): Elk-1 protein domains required for direct and SRF-assisted DNA-binding. Nucleic Acids Res 20: 3317–3324PubMedGoogle Scholar
  78. Janknecht R, Nordheim A (1993): Gene regulation by Ets proteins. Biochim Biophys Acta 1155: 346–356PubMedGoogle Scholar
  79. Janknecht R, Ernst WH, Houthaeve T, Nordheim A (1993a): C-terminal phosphorylation of the serum-response factor. Eur J Biochem 216: 469–475PubMedGoogle Scholar
  80. Janknecht R, Ernst WH, Pingoud V, Nordheim A (1993b): Activation of ternary complex factor Elk-1 by MAP kinases. EMBO J 12: 5097–5104PubMedGoogle Scholar
  81. Janknecht R, Hipskind RA, Houthaeve T, Nordheim A, Stunnenberg HG (1992): Identification of multiple SRF N-terminal phosphorylation sites affecting DNA binding properties. EMBO J 11: 1045–1054PubMedGoogle Scholar
  82. Janknecht R, Zinck R, Ernst WH, Nordheim A (1994): Functional dissection of the transcription factor Elk-1. Oncogene 9: 1273–1278PubMedGoogle Scholar
  83. Johansen F-E, Prywes R (1993): Identification of transcriptional activation and inhibitory domains in serum response factor (SRF) by using GAL4-SRF constructs. Mol Cell Biol 13: 4640–4647PubMedGoogle Scholar
  84. Joly M, Kazlauskas A, Fay FS, Corvera S (1994): Disruption of PDGF receptor trafficking by mutation of its PI-3 kinase binding sites. Science 263: 684–687PubMedGoogle Scholar
  85. Joseph L, J Le Beau MM, Jamieson GA, Acharya S, Shows TB, Rowley JD, Sukhatme VP (1988): Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with “zinc-binding finger” structure. Proc Natl Acad Sci USA 85: 7164–7168PubMedGoogle Scholar
  86. Kahan C, Seuwen K, Meloche S, Pouysségur J (1992): Coodinate biphasic activation of p44 Mitogen-Activated protein kinases and S6 kinase by growth factors in Hamster fibroblasts. J Biol Chem 267: 13369–13375PubMedGoogle Scholar
  87. Kaibuchi K, Fukumoto Y, Oku N, Hori Y, Yamamoto T, Toyoshima K, Takai Y (1989): Activation of the serum response element and 12–O-tetra-decanoyl-13-acetate response element by the activated c-raf-1 protein in a manner independent of protein kinase C. J Biol Chem 264: 20855–20858PubMedGoogle Scholar
  88. Kapeller R, Prasad KVS, Janssen O, Hou W, Schaffhausen BS, Rudd CE, Cantley LC (1994): Identification of two SH3-binding motifs in the regulatory subunit of phosphatidylinositol 3-kinase. J Biol Chem 269: 1927–1933PubMedGoogle Scholar
  89. Kardalinou E, Zhelev N, Hazzalin CA, Mahadevan LC (1994): Anisomycin and rapamycin define an area upstream of p70/85S6k containing a bifurcation to histone H3-HMG-like protein phosphorylation and c-fos-c-jun induction. Mol Cell Biol 14: 1066–1074PubMedGoogle Scholar
  90. Keyse SM, Emslie EA (1992): Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase. Nature 359: 644–647PubMedGoogle Scholar
  91. Kishimoto T, Taga T, Akira S (1994): Cytokine signal transduction. Cell 76: 253–262PubMedGoogle Scholar
  92. König H (1991): Cell-type specific multiprotein complex formation over the c-fos serum response element in vivo: ternary complex formation is not required for the induction of c-fos. Nucleic Acids Res 19: 3607–3611PubMedGoogle Scholar
  93. König H, Ponta H, Rahmsdorf U, Büscher M, Schönthal A, Rahmsdorf HJ, Herrlich P (1989): Autoregulation of fos: the dyad symmetry element as the major target of repression. EMBO J 8: 2559–2566PubMedGoogle Scholar
  94. Kruijer W, Cooper JA, Hunter T, Verma IM (1984): Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature 312: 711–716PubMedGoogle Scholar
  95. Lang A, Fincham VJ, Wyke JA (1993): Factors influencing physiological variations in the actitvity of the Rous Sarcoma Virus long terminal repeat. Virol 196: 564–575Google Scholar
  96. Lange-Carter CA, Pleiman CM, Gardner AM, Blumer KJ, Johnson GL (1993): A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science 260: 315–319PubMedGoogle Scholar
  97. Latinkic BV, O’Brien TP, Lau LF (1991): Promoter function and structure of the growth factor-inducible immediate early gene cyról. Nucl Acids Res 19: 3261–3267Google Scholar
  98. Lau LF, Nathans D (1985): Identification of a set of genes expressed during the G0/Gi transition of cultured mouse cells. EMBO J 4: 3145–3151PubMedGoogle Scholar
  99. Lazo PS, Dorfman K, Noguchi T, Mattei MG, Bravo R (1992): Structure and mapping ofthzfosB gene. FosB downregulates the activity of the fosB promoter. Nucl Acids Res 20: 343–350PubMedGoogle Scholar
  100. Lee T-C, Chow K-L, Fang P, Schwartz RJ (1991): Activation of skeletal α-actin gene transcription: The cooperative formation of serum response factor-binding complexes over positive cw-acting promoter serum response elements displaces a negative-acting nuclear factor enriched in replicating myoblasts and nonmyogenic cells. Mol Cell Biol 11: 5090–5100PubMedGoogle Scholar
  101. Lefkowitz RJ (1993): G protein-coupled receptor kinases. Cell 74: 409–412PubMedGoogle Scholar
  102. Lemaire P, Revelant O, Bravo R, Charnay P (1988): Two mouse genes encoding potential transcription factors with identical DNA-binding domains are activated by growth factors in cultured cells. Proc Natl Acad Sci USA 85: 4691–4695PubMedGoogle Scholar
  103. Li Y, Jaiswal K (1992): Identification of JunB as third member in human antioxidant response element-nuclear proteins complex. Biochem Biophys Res Comm 188: 992–996PubMedGoogle Scholar
  104. Lin X, Wang Z, Gu L, Deuel TF (1992): Functional analysis of the human platelet-derived growth factor A-chain promoter region. J Biol Chem 267: 25614–25619PubMedGoogle Scholar
  105. Liu S-H, Ma J-T, Yueh AY, Lees-Miller SP, Anderson CW, Ng S-Y (1993): The carboxyl-terminal transactivation domain of human serum response factor contains DNA-activated protein kinase phosphorylation sites.J Biol Chem 268:21147–21154PubMedGoogle Scholar
  106. Lowy DR, Willumsen BM (1993): Function and regulation of Ras. Annu Rev Biochem 62: 851–891PubMedGoogle Scholar
  107. MacNicol AM, Muslin AJ, Williams LT (1993): Raf-1 kinase is essential for early Xenopus development and mediates the induction of mesoderm by FGF. Cell 73: 571–583PubMedGoogle Scholar
  108. Manak JR, Prywes R (1991): Mutation of serum response factor phosphorylation sites and the mechanism by which its DNA-binding activity is increased by casein kinase IL Mol Cell Biol 11: 3652–3659PubMedGoogle Scholar
  109. Marais RM, Hsuan JJ, McGuidan C, Wynne J, Treisman R (1992): Casein kinase II phosphorylation increases the rate of serum response factor-binding site exchange. EMBO J 11: 97–105PubMedGoogle Scholar
  110. Marais R, Wynne J, Treisman R (1993): The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell 73: 381–393PubMedGoogle Scholar
  111. Marshall CJ (1994): MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr Opin Genet Dev 4: 82–89PubMedGoogle Scholar
  112. Marx J (1993): Two major signal pathways linked. Science 262: 988–990PubMedGoogle Scholar
  113. McCormick F (1993): How receptors turn Ras on. Nature 363: 15–16PubMedGoogle Scholar
  114. Metz R, Zif TE (1991): The helix-loop-helix protein rE12 and the C/EBP-related factor rNFIL-6 bind to neighboring sites within the c-fos serum response element. Oncogene 6: 2165–2178PubMedGoogle Scholar
  115. Mitchell RL, Zokas L, Schreiber RD, Verma IM (1985): Rapid induction of the 68 MA Cahill, R Janknecht and A Nordhei expression of proto-oncogene fos during human monocyte differentiation. Cell 40:209–217PubMedGoogle Scholar
  116. Miwa T, Boxer L, Kedes L (1987): CArG boxes in the human cardiac α-actin gene are core binding sites for positive trans-acting regulatory factors. Proc Natl Acad Sci USA 84: 6702–6706PubMedGoogle Scholar
  117. Mohun TJ, Chambers AE, Towers N, Taylor MV (1991): Expression of genes encoding the transcription factor SRF during early development of Xenopus laevis: identification of a CArG box-binding activity as SRF. EMBO J 10: 933–940PubMedGoogle Scholar
  118. Mohun TJ, Garrett N, Treisman RH (1987): Xenopus cytoskeletal actin and human c-fos gene promoters share a conserved protein binding site. EMBO J 6: 667–673PubMedGoogle Scholar
  119. Mohun TJ, Taylor MV, Garrett N, Gurdon JB (1989): The CArG promoter sequence is necessary for muscle-specific transcription of the cardiac actin gene in Xenopus embryos. EMBO J 8: 1153–1161PubMedGoogle Scholar
  120. Moisseyeva EP, Weiler PA, Zhidkova NI, Corben EB, Patel B, Jasinka I, Koteliansky VE, Critchley DR (1993): Organization of the human gene encoding the cytoskeletal protein vinculin and the sequence of the vinculin promoter. J Biol Chem 268: 4318–4325Google Scholar
  121. Montminy M, (1993): Trying on a new pair of SH2s. Science 261: 1694–1695PubMedGoogle Scholar
  122. Moodie SA, Wolfman A (1994): The 3Rs of life: Ras, Raf and growth regulation. Trends Gen 10: 44–48Google Scholar
  123. Mueller CGF, Nordheim A (1991): A protein domain conserved between yeast MCM1 and human SRF directs ternary complex formation. EMBO J 10: 4219–4229PubMedGoogle Scholar
  124. Müller R, Bravo R, Burckhardt J, Curran T (1984): Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 312: 716–720PubMedGoogle Scholar
  125. Musacchio A, Gibson T, Rice P, Thompson J, Saraste M (1993): The pH domain: a common piece in the structural patchwork of signalling proteins. Trends Biochem Sci 18: 343–348PubMedGoogle Scholar
  126. Nakanishi H, Brewer KA, Exton JG (1993): Activation of the ζ-isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 268: 13–16PubMedGoogle Scholar
  127. Natesan S, Gilman MZ (1993): DNA bending and orientation-dependent function of YY1 in the c-fos promoter. Genes Dev 7: 2497–2509PubMedGoogle Scholar
  128. Nebreda AR, Hill C, Gomez N, Cohen P, Hunt T (1993): The protein kinase mos activates MAP kinase kinase in vitro and stimulates the MAP kinase pathway in mammalian somatic cells in vivo. FEBS Lett 333: 183–187PubMedGoogle Scholar
  129. Neiman AM (1993): Conservation and reiteration of a kinase cascade. Trends Gen 9: 390–394Google Scholar
  130. Nordheim A, Janknecht R, Hipskind R (1994): Transcriptional regulation of the human c-fos proto-oncogene. In: Cellular and Viral fos Genes, Angel P, Herrich P, eds. CRC Press, Boca Raton (in press)Google Scholar
  131. Norman C, Runswick M, Pollock R, Treisman R (1988): Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell 55: 989–1003PubMedGoogle Scholar
  132. Orita S, Makino K, Kawamoto T, Niwa H, Sugiyama H, Kakanuga T (1989): Identification of a site that mediates transcriptional response of the human β actin gene to serum factors. Gene 75: 13–19PubMedGoogle Scholar
  133. Otsu M, Terada Y, Okayama H (1993): Isolation of two members of the rat MAP kinase kinase gene family. FEBS 320: 246–250Google Scholar
  134. Parker PJ, Hemmings BA, Gierschik P (1994): PH domains and phospholipases — a meaningful relationship? Trends Biochem Sci 19: 54–55PubMedGoogle Scholar
  135. Parmentier M, Libert F, Perret J, Eggerickx D, Ledent C, Schurmans S, Raspe E, Dumont JE, Vassart G (1993): Cloning and characterization of G protein-coupled receptors. Advances in Second Messenger and Phosphoprotein Research 28: 11–18PubMedGoogle Scholar
  136. Pelech SL, Sanghera JS (1992): Mitogen-activated protein kinases: versatile transducers for cell signaling. Trends Biochem Sci 17: 233–238PubMedGoogle Scholar
  137. Perez-Albuerne ED, Schatteman G, Sanders LK, Nathans D (1993): Transcriptional regulatory elements downstream of the junB gene. Proc Natl Acad Sci USA 90: 11960–11964PubMedGoogle Scholar
  138. Perrimon N (1993): The Torso receptor protein-tyrosine kinase signaling pathway: an endless story. Cell 74: 219–222PubMedGoogle Scholar
  139. Phan-Dinh-Tuy F, Tuil D, SchweighofTer F, Pinset C, Kahn A, Minty A (1988): The CC.Ar.GG box: a protein-binding site common to transcription-regulatory proteins of the cardiac actin, c-fos, and interleukin-2 receptor genes. Eur J Biochem 173: 507–515PubMedGoogle Scholar
  140. Pingoud V, Zinck R, Hipskind RA, Janknecht R, Nordheim A (1994): Heterogeneity of ternary complex factors in HeLa cell nuclear extracts. J Biol Chem: in pressGoogle Scholar
  141. Prywes R, Roeder RG (1986): Inducible binding of a factor to the c-fos enhancer. Cell 47: 777–784PubMedGoogle Scholar
  142. Qian N-X, Winitz S, Johnson GL (1993): Epitope-tagged Gqa subunits: expression of GTPase-deficient α subunits persistently stimulates phosphatidylinositol-specific phospholipase C but not mitogen-activated protein kinase activity regulated by the m1 muscarinic acetylcholine receptor. Proc Natl Acad Sci USA 90: 4077–4081PubMedGoogle Scholar
  143. Rao VN, Reddy ESP (1992a): A divergent eto-related protein, Elk-1, recognizes similar c-ets-l proto-oncogene target sequences and acts as a transcriptional activator. Oncogene 7: 65–70PubMedGoogle Scholar
  144. Rao VN, Reddy ESP (1992b): elk-1 domains responsible for autonomous DNA binding, SRE:SRF interaction and negative regulation of DNA binding. Oncogene 7: 2335–2340Google Scholar
  145. Rao VN, Reddy ESP (1993): Aelk-1, a variant of Elk-l, fails to interact with the serum response factor and binds to DNA with modulated specificity. Cancer Res 53: 215–220PubMedGoogle Scholar
  146. Reason AJ, Morris HR, Panico M, Marais R, Treisman RH, Haltiwanger RS, Hart GW, Kelly WG, Dell A (1992): Localization of O-GlcNAc modification on the serum response transcription factor. J Biol Chem 261: 16911–16921Google Scholar
  147. Rivera VM, Greenberg ME (1990): Growth factor-induced gene expression: the ups and downs of c-fos regulation. New Biol 2: 751–758PubMedGoogle Scholar
  148. Rivera VM, Miranti CK, Misra RP, Ginty DD, Chen R-H, Blenis J, Greenberg ME (1993): A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity. Mol Cell Biol 13: 6260–6273PubMedGoogle Scholar
  149. Rohan PJ, Davis P, Moskaluk CA, Kearns M, Krutzsch H, Siebenlist U, Kelly K (1993): PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase. Science 259: 1763–1766PubMedGoogle Scholar
  150. Rossomando AJ, Dent P, Sturgill TW, Marshak DR (1994): Mitogen-activated protein kinase kinase 1 (MKK1) is negatively regulated by threonine phosphorylation. Mol Cell Biol 14: 1594–1602PubMedGoogle Scholar
  151. Ryan WA Jr, Franza BR Jr, Gilman MZ (1989): Two distinct cellular phosphoproteins bind to the c-fos serum response element. EMBO J 8: 1785–1792PubMedGoogle Scholar
  152. Sato N, Sakamaki K, Terada N, Arai K-i, Miyajima A (1993): Signal transduction by the high affinity GM-CSF receptor: two distinct cytoplasmic regions of the common β subunit responsible for different signaling. EMBO J 12: 4181–4189PubMedGoogle Scholar
  153. Satoh T, Nakafuku M, Kaziro Y (1992): Function of Ras as a Molecular Switch in Signal Transduction. J Biol Chem 267: 24149–24152PubMedGoogle Scholar
  154. Schalasta G, Doppler C (1990): Inhibition of c-fos transcription and phosphorylation of the serum response factor by an inhibitor of phospholipase C-type reactions. Mol Cell Biol 10: 5558–5561PubMedGoogle Scholar
  155. Schröter H, Mueller CGF, Meese K, Nordheim A (1990): Synergism in ternary complex formation between the dimeric glycoprotein q67SRF, polypeptide p62TCF and the c-fos serum response element. EMBO J 9: 1123–1130PubMedGoogle Scholar
  156. Schulman H, Lou LL (1989): Multifunctional Ca2+-calmodulin-dependent protein kinase: domain structure and regulation. Trends Biochem Sci 14: 62–66PubMedGoogle Scholar
  157. Schwarz-Sommer Z, Huijser P, Nacken W, Saedler H, Sommer H (1990): Genetic control of flower development by homeotic genes in Antirrhinum majus. Science 250: 931–936PubMedGoogle Scholar
  158. Seger R, Seger D, Lozeman FJ, Ahn NG, Graves LM, Campbell JS, Ericsson L, Harrylock M, Jensen AM, Krebs EG (1992): Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases. J Biol Chem 267: 25628–25631PubMedGoogle Scholar
  159. Sharrocks AD, Gille H, Shaw PE (1993): Identification of amino acids essential for DNA binding and dimerization in p67SRF: implications for a novel DNA-binding motif. Mol Cell Biol 13: 123–132PubMedGoogle Scholar
  160. Shaw PE (1992): Ternary complex formation over the c-fos serum response element: p62TCF exhibits dual component specificity with contacts to DNA and an extended structure in the DNA-binding domain of p67SRF. EMBO J 11: 3011–3019PubMedGoogle Scholar
  161. Shaw PE, Frasch S, Nordheim A (1989a): Repression of c-fos transcription is mediated through p67SRF bound to the SRE. EMBO J 8: 2567–2574PubMedGoogle Scholar
  162. Shaw PE, Schröter H, Nordheim A (1989b): The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter. Cell 56: 563–572PubMedGoogle Scholar
  163. Shibuya H, Yoneyama M, Ninomiya-Tsuji J, Matsumoto K, Taniguchi T (1993): IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role for c-myc. Cell 70: 57–67Google Scholar
  164. Sternberg PW, Golden A, Han M (1993): Role of the raf proto-oncogene during Caenorhabditis elegans vulval development. Phil Trans Roy Soc (Lond) B 340: 259–265Google Scholar
  165. Sternweis PC, Smreka AV (1992): Regulation of phospholipase C by G proteins. Trends Biochem Sci 17: 502–506PubMedGoogle Scholar
  166. Stoflet ES, Schmidt LJ, Elder PK, Korf GM, Foster DN, Strauch AR, Getz MJ (1992): Activation of a muscle-specific actin gene promoter in serum-stimulated fibroblasts. Mol Biol Cell 3: 1073–1083PubMedGoogle Scholar
  167. Subramaniam M, Schmidt LJ, Crutchfield CE III, Getz MJ (1989): Negative regulation of serum-responsive enhancer elements. Nature 340: 64–66PubMedGoogle Scholar
  168. Sukhatme VP, Cao X, Chang LC, Tsai-Morris C-H, Stamenkovich D, Ferreira PCP, Cohen DR, Edwards SA, Shows TB, Curran T, LeBeau MM, Adamson ED (1988): A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell 53: 37–43PubMedGoogle Scholar
  169. Sun H, Charles CH, Lau LF, Tonks NK (1993): MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell 75: 487–493PubMedGoogle Scholar
  170. Suzuki T, Hirai H, Fujisawa J-I, Fujita T, Yoshida M (1993): A trans-activator Tax of human T-cell leukemia virus type 1 binds to NF-кB p50 and serum response factor (SRF) and associates with enhancer DNAs of the NF-кB site and CArG box. Oncogene 8: 2391–2397PubMedGoogle Scholar
  171. Treisman R (1985): Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5′ element and c-fos 3′ sequences. Cell 42: 889–902PubMedGoogle Scholar
  172. Treisman R (1986): Identification of a protein-binding site that mediates transcription response of the c-fos gene to serum factors. Cell 46: 567–574PubMedGoogle Scholar
  173. Treisman R (1987): Identification and purification of a polypeptide that binds the c-fos serum response element. EMBO J 6: 2711–2717PubMedGoogle Scholar
  174. Treisman R (1992): Structure and function of serum response factor. In: Transcriptional Regulation, McKnight SL, Yamamoto KR, eds. Cold Spring Harbor: Cold Spring Harbor Laboratory PressGoogle Scholar
  175. Treisman R (1994): Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev 4: 96–101PubMedGoogle Scholar
  176. Treisman R, Ammerer G (1992): The SRF and MCMl transcription factors. Curr Opin Genet Dev 2: 221–226PubMedGoogle Scholar
  177. Treisman R, Marais R, Wynne J (1992): Spatial flexibility in ternary complexes between SRF and its accessory proteins. EMBO J 11: 4631–4640PubMedGoogle Scholar
  178. Velcich A, Ziff EB (1990): Functional analysis of an isolated fos promoter element with AP-1 site homology reveals cell type-specific transcriptional properties. Mol Cell Biol 10: 6273–6282PubMedGoogle Scholar
  179. Wang Z-Q, Ovitt C, Grigoriadis E, Möhle-Steinlein U, Rüther U, Wagner EF (1992): Bone and haematopoietic defects in mice lacking c-fos. Nature 360: 741–745PubMedGoogle Scholar
  180. Ward Y, Gupta S, Jensen P, Wartmann M, Davis RJ, Kelly K (1994): Control of MAP kinase activation by the mitogen-induced threonine/tyrosine phosphatase PAC1. Nature 367: 651–654PubMedGoogle Scholar
  181. Wasylyk B, Hahn SL, Giovane A (1993): The Ets family of transcription factors. Eur J Biochem 211: 7–18PubMedGoogle Scholar
  182. Weiss A, Littman DR (1994): Signal transduction by lymphocyte antigen receptors. Cell 76: 263–274PubMedGoogle Scholar
  183. Williamson MP, (1994): The structure and function of proline-rich regions in proteins. Biochem J 297: 249–260PubMedGoogle Scholar
  184. Winitz S, Russell M, Qian N-X, Gardner A, Dwyer L, Johnson GL (1993): Involvement of Ras and Raf in the Gi-coupled acetylcholine muscarinic m2 receptor activation of mitogen-activated protein (MAP) kinase kinase and MAP kinase. J Biol Chem 268: 19196–19199PubMedGoogle Scholar
  185. Wu J, Harrison JK, Vincent LA, Haystead C, Haystead TAJ, Michel H, Hunt DF, Lynch KR, Sturgill TW (1993): Molecular structure of a protein-tyrosine/threonine kinase activating p42 mitogen-activated protein (MAP) kinase: MAP kinase kinase. Proc Natl Acad Sci USA 90: 173–177PubMedGoogle Scholar
  186. Yoshida T, Suzuki T, Sato H, Nishina H, Iba H (1993): Analysis of fra2 gene expression. Nucl Acids Res 21: 2715–2721PubMedGoogle Scholar
  187. Zachow K, Conklin KF (1992): CArG, CCAAT, and CCAAT-like protein binding sites in avian retrovirus long terminal repeat enhancers. J Virol 66: 1959–1970PubMedGoogle Scholar
  188. Zhang X-f, Settleman J, Kyriakis JM, Takeuchi-Suzuki E, Elledge SJ, Marshall MS, Bruder JT, Rapp UR, Avruch J (1993): Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1. Nature 364: 308–313PubMedGoogle Scholar
  189. Zheng C-F, Guan K-L (1993a): Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. J Biol Chem 268: 11435–11439PubMedGoogle Scholar
  190. Zheng C-F, Guan K-L (1993b): Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases. J Biol Chem 268: 23933–23939PubMedGoogle Scholar
  191. Zheng, C-F, Guan K-L (1994): Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. EMBO J 13: 1123–1131PubMedGoogle Scholar
  192. Zhu H, Prywes R (1992): Identification of a coactivator that increases activation of transcription by serum response factor and GAL4-VP16 in vitro. Proc Natl Acad Sci USA 89: 5191–5295Google Scholar
  193. Zidovetzki R, Lester DS (1992): The mechanism of activation of protein kinase C: a biophysical perspective. Biochim Biophys Acta 1134: 261–272PubMedGoogle Scholar
  194. Zinck R, Hipskind RA, Pingoud V, Nordheim A (1993): c-fos transcriptional activation and repression correlate temporally with the phosphorylation status of TCF. EMBO J 12: 2377–2387PubMedGoogle Scholar

Copyright information

© Birkhäuser Boston 1995

Authors and Affiliations

  • Michael A. Cahill
  • Ralf Janknecht
  • Alfred Nordheim

There are no affiliations available

Personalised recommendations