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PMID: 9891045 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Complementation of defective colony-stimulating factor 1 receptor signaling and mitogenesis by Raf and v-Src.

Molecular and cellular biology ·Vol. 19 ·No. 2 ·1999-02-00 ·Pages 1101-15

Aziz N, Cherwinski H, McMahon M

Abstract

Ras-activated signal transduction pathways are implicated in the control of cell proliferation, differentiation, apoptosis, and tumorigenesis, but the molecular mechanisms mediating these diverse functions have yet to be fully elucidated. Conditionally active forms of Raf, v-Src, and MEK1 were used to identify changes in gene expression that participate in oncogenic transformation, as well as in normal growth control. Activation of Raf, v-Src, and MEK1 led to induced expression of c-Myc and cyclin D1. Induction of c-Myc mRNA by Raf was an immediate-early response, whereas the induction of cyclin D1 mRNA was delayed and inhibited by cycloheximide. Raf activation also resulted in the induction of an established c-Myc target gene, ornithine decarboxylase (ODC). ODC induction by Raf was mediated, in part, by tandem E-boxes contained in the first intron of the gene. Activation of the human colony-stimulating factor 1 (CSF-1) receptor in NIH 3T3 cells leads to activation of the mitogen-activated protein (MAP) kinase pathway and induced expression of c-Fos, c-Myc, and cyclin D1, leading to a potent mitogenic response. By contrast, a mutated form of this receptor fails to activate the MAP kinases or induce c-Myc and cyclin D1 expression and fails to elicit a mitogenic response. The biological significance of c-Myc and cyclin D1 induction by Raf and v-Src was confirmed by the demonstration that both of these protein kinases complemented the signaling and mitogenic defects of cells expressing this mutated form of the human CSF-1 receptor. Furthermore, the induction of c-Myc and cyclin D1 by oncogenes and growth factors was inhibited by PD098059, a specific MAP kinase kinase (MEK) inhibitor. These data suggest that the Raf/MEK/MAP kinase pathway plays an important role in the regulation of c-Myc and cyclin D1 expression in NIH 3T3 cells. The ability of oncogenes such as Raf and v-Src to regulate the expression of these proteins reveals new lines of communication between cytosolic signal transducers and the cell cycle machinery.

MeSH Terms
3T3 Cells Animals Cell Division Cyclin D1/genetics Enzyme Activation Gene Expression Regulation Genes, src Genetic Complementation Test Humans MAP Kinase Kinase 1 Mice Mitogen-Activated Protein Kinase Kinases Mutation Ornithine Decarboxylase/genetics Protein Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins c-myc/genetics Proto-Oncogene Proteins c-raf/genetics,metabolism RNA, Messenger/genetics,metabolism Receptor, Macrophage Colony-Stimulating Factor/genetics,metabolism Signal Transduction Transfection src-Family Kinases/genetics,metabolism
Chemicals
Proto-Oncogene Proteins c-myc RNA, Messenger Cyclin D1 Protein-Tyrosine Kinases Receptor, Macrophage Colony-Stimulating Factor src-Family Kinases Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-raf MAP Kinase Kinase 1 MAP2K1 protein, human Map2k1 protein, mouse Mitogen-Activated Protein Kinase Kinases Ornithine Decarboxylase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Aziz N
Department of Cell Signaling, DNAX Research Institute, Palo Alto, California 94304-1104, USA.
Cherwinski H
McMahon M
References (138)
138 references, click to expand
  1. c-myc hypermutation in Burkitt's lymphoma.
    Leuk Lymphoma. 1992 Dec;8(6):431-9 PMID: 1297477
  2. Raf-1 activates MAP kinase-kinase.
    Nature. 1992 Jul 30;358(6385):417-21 PMID: 1322500
  3. Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro.
    Science. 1992 Sep 4;257(5075):1404-7 PMID: 1326789
  4. Multiple DNA elements responsible for transcriptional regulation of the ornithine decarboxylase gene by protein kinase A.
    J Biol Chem. 1992 Sep 15;267(26):18866-73 PMID: 1356108
  5. Both p21ras and pp60v-src are required, but neither alone is sufficient, to activate the Raf-1 kinase.
    Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2922-6 PMID: 1372995
  6. Myc and Max proteins possess distinct transcriptional activities.
    Nature. 1992 Oct 1;359(6394):426-9 PMID: 1406956
  7. Mitogenic signaling by colony-stimulating factor 1 and ras is suppressed by the ets-2 DNA-binding domain and restored by myc overexpression.
    Mol Cell Biol. 1992 Dec;12(12):5355-62 PMID: 1448070
  8. Raf functions downstream of Ras1 in the Sevenless signal transduction pathway.
    Nature. 1992 Dec 10;360(6404):600-3 PMID: 1461284
  9. c-myc antisense oligonucleotides inhibit the colony-forming capacity of Colo 320 colonic carcinoma cells.
    J Clin Invest. 1992 May;89(5):1523-7 PMID: 1569190
  10. Multiple promoter elements govern expression of the human ornithine decarboxylase gene in colon carcinoma cells.
    Nucleic Acids Res. 1992 May 25;20(10):2581-90 PMID: 1598217
  11. Regulation of p21ras by GTPase activating proteins and guanine nucleotide exchange proteins.
    Curr Opin Genet Dev. 1992 Feb;2(1):13-8 PMID: 1633420
  12. Signal transduction during C. elegans vulval induction.
    Trends Genet. 1991 Nov-Dec;7(11-12):366-71 PMID: 1668188
  13. Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases.
    Nature. 1991 Sep 12;353(6340):170-3 PMID: 1716348
  14. A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression.
    J Biol Chem. 1991 Dec 15;266(35):23521-4 PMID: 1748630
  15. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle.
    Cell. 1991 May 17;65(4):701-13 PMID: 1827757
  16. Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signalling.
    Nature. 1991 Sep 26;353(6342):361-3 PMID: 1833648
  17. An inhibitory mutant of c-Raf-1 blocks v-Src-induced activation of the Egr-1 promoter.
    J Biol Chem. 1991 Nov 5;266(31):20594-7 PMID: 1939108
  18. Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region.
    Science. 1991 Jan 11;251(4990):186-9 PMID: 1987636
  19. Raf-1 protein kinase is required for growth of induced NIH/3T3 cells.
    Nature. 1991 Jan 31;349(6308):426-8 PMID: 1992343
  20. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc.
    Science. 1991 Mar 8;251(4998):1211-7 PMID: 2006410
  21. Inhibition of v-src-induced transformation by a GTPase-activating protein.
    Mol Cell Biol. 1991 May;11(5):2812-8 PMID: 2017178
  22. Suppression of src transformation by overexpression of full-length GTPase-activating protein (GAP) or of the GAP C terminus.
    Mol Cell Biol. 1991 May;11(5):2819-25 PMID: 2017179
  23. Depletion of c-myc with specific antisense sequences reverses the transformed phenotype in ras oncogene-transformed NIH 3T3 cells.
    Mol Cell Biol. 1991 Jul;11(7):3699-710 PMID: 2046673
  24. raf oncogenes in carcinogenesis.
    Crit Rev Oncog. 1990;2(1):1-8 PMID: 2091747
  25. A point mutation at tyrosine-809 in the human colony-stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity, association with phosphatidylinositol 3-kinase, or induction of c-fos and junB genes.
    Proc Natl Acad Sci U S A. 1990 Sep;87(17):6738-42 PMID: 2168557
  26. Tumorigenesis and male sterility in transgenic mice expressing a MMTV/N-ras oncogene.
    Oncogene. 1990 Oct;5(10):1491-7 PMID: 2174525
  27. Molecular genetics of polyamine synthesis in eukaryotic cells.
    Trends Biochem Sci. 1990 Apr;15(4):153-8 PMID: 2187296
  28. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line.
    Nucleic Acids Res. 1990 Jun 25;18(12):3587-96 PMID: 2194165
  29. Sequence-specific DNA binding by the c-Myc protein.
    Science. 1990 Nov 23;250(4984):1149-51 PMID: 2251503
  30. Augmented mitogenic responsiveness to epidermal growth factor in murine fibroblasts that overexpress pp60c-src.
    Mol Cell Biol. 1988 Jan;8(1):497-501 PMID: 2447487
  31. L-myc cooperates with ras to transform primary rat embryo fibroblasts.
    Mol Cell Biol. 1988 Jun;8(6):2668-73 PMID: 2457153
  32. ras oncogenes in human cancer: a review.
    Cancer Res. 1989 Sep 1;49(17):4682-9 PMID: 2547513
  33. Mouse NIH 3T3 cells expressing human colony-stimulating factor 1 (CSF-1) receptors overgrow in serum-free medium containing human CSF-1 as their only growth factor.
    Proc Natl Acad Sci U S A. 1989 Oct;86(20):7924-7 PMID: 2554296
  34. p21H-ras-induced morphological transformation and increases in c-myc expression are independent of functional protein kinase C.
    EMBO J. 1989 Apr;8(4):1099-104 PMID: 2663469
  35. The first seven amino acids encoded by the v-src oncogene act as a myristylation signal: lysine 7 is a critical determinant.
    Mol Cell Biol. 1988 Jun;8(6):2435-41 PMID: 2841581
  36. Requirement for c-ras proteins during viral oncogene transformation.
    Nature. 1986 Apr 10-16;320(6062):540-3 PMID: 2938016
  37. Synergism of v-myc and v-Ha-ras in the in vitro neoplastic progression of murine lymphoid cells.
    Mol Cell Biol. 1986 Sep;6(9):3221-31 PMID: 3023969
  38. The mechanisms of ornithine decarboxylase deregulation in c-Ha-ras oncogene-transformed NIH 3T3 cells.
    J Biol Chem. 1988 Mar 25;263(9):4500-7 PMID: 3279036
  39. Transformation by raf and myc oncogenes.
    Princess Takamatsu Symp. 1986;17:55-74 PMID: 3332021
  40. Mouse ornithine decarboxylase gene: cloning, structure, and expression.
    Proc Natl Acad Sci U S A. 1988 Apr;85(7):2200-4 PMID: 3353375
  41. N-myc can cooperate with ras to transform normal cells in culture.
    Proc Natl Acad Sci U S A. 1985 Aug;82(16):5455-9 PMID: 3860871
  42. Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells.
    Mol Cell Biol. 1984 Nov;4(11):2486-97 PMID: 6513926
  43. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor.
    Cell. 1983 Dec;35(3 Pt 2):603-10 PMID: 6606489
  44. Phosphorylation of Raf by ceramide-activated protein kinase.
    Nature. 1995 Nov 16;378(6554):307-10 PMID: 7477354
  45. Signal transduction. Beating a path to Myc.
    Nature. 1995 Nov 30;378(6556):438-9 PMID: 7477397
  46. Myc but not Fos rescue of PDGF signalling block caused by kinase-inactive Src.
    Nature. 1995 Nov 30;378(6556):509-12 PMID: 7477410
  47. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo.
    J Biol Chem. 1995 Nov 17;270(46):27489-94 PMID: 7499206
  48. v-src induces prostaglandin synthase 2 gene expression by activation of the c-Jun N-terminal kinase and the c-Jun transcription factor.
    J Biol Chem. 1995 Nov 17;270(46):27622-8 PMID: 7499226
  49. Ras is not required for the interleukin 3-induced proliferation of a mouse pro-B cell line, BaF3.
    J Biol Chem. 1995 Nov 17;270(46):27880-6 PMID: 7499262
  50. A target for Src in mitosis.
    Nature. 1994 Apr 28;368(6474):871-4 PMID: 7512695
  51. Mesoderm induction in Xenopus caused by activation of MAP kinase.
    Nature. 1995 Jul 6;376(6535):58-62 PMID: 7541116
  52. Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation.
    EMBO J. 1995 Jul 3;14(13):3136-45 PMID: 7542586
  53. Requirement for Src family protein tyrosine kinases in G2 for fibroblast cell division.
    Science. 1995 Sep 15;269(5230):1567-9 PMID: 7545311
  54. Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions.
    J Biol Chem. 1995 Oct 6;270(40):23589-97 PMID: 7559524
  55. Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display different biological and biochemical properties in NIH 3T3 cells.
    Mol Cell Biol. 1995 Nov;15(11):6430-42 PMID: 7565795
  56. Rescue of defective mitogenic signaling by D-type cyclins.
    Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6837-41 PMID: 7624328
  57. Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes.
    Genes Dev. 1995 Aug 15;9(16):1953-64 PMID: 7649477
  58. Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor.
    EMBO J. 1993 Mar;12(3):943-50 PMID: 7681396
  59. Raf-1 kinase is essential for early Xenopus development and mediates the induction of mesoderm by FGF.
    Cell. 1993 May 7;73(3):571-83 PMID: 7683975
  60. Production of high-titer helper-free retroviruses by transient transfection.
    Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392-6 PMID: 7690960
  61. Critical tyrosine residues regulate the enzymatic and biological activity of Raf-1 kinase.
    Mol Cell Biol. 1993 Nov;13(11):7170-9 PMID: 7692235
  62. Transcriptional activation by Myc is under negative control by the transcription factor AP-2.
    EMBO J. 1995 Apr 3;14(7):1508-19 PMID: 7729426
  63. Regulation of c-fos expression in transgenic mice requires multiple interdependent transcription control elements.
    Neuron. 1995 Feb;14(2):241-52 PMID: 7857636
  64. Regulation of rat ornithine decarboxylase promoter activity by binding of transcription factor Sp1.
    J Biol Chem. 1995 Mar 3;270(9):4341-8 PMID: 7876196
  65. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells.
    Cell. 1994 Jun 17;77(6):841-52 PMID: 7911739
  66. The Ras/Raf signaling pathway is required for progression of mouse embryos through the two-cell stage.
    Mol Cell Biol. 1994 Oct;14(10):6655-62 PMID: 7935384
  67. MAP kinase binds to the NH2-terminal activation domain of c-Myc.
    FEBS Lett. 1994 Oct 24;353(3):281-5 PMID: 7957875
  68. Human neuroblastoma: amplification of the N-myc oncogene and loss of a putative cancer-preventing gene on chromosome 1p.
    Recent Results Cancer Res. 1994;135:7-16 PMID: 8047699
  69. Transformation of mammalian cells by constitutively active MAP kinase kinase.
    Science. 1994 Aug 12;265(5174):966-70 PMID: 8052857
  70. Direct transcriptional stimulation of the ornithine decarboxylase gene by Fos in PC12 cells but not in fibroblasts.
    Mol Cell Biol. 1993 Aug;13(8):4657-69 PMID: 8101634
  71. Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense oligodeoxynucleotides.
    J Clin Invest. 1994 Feb;93(2):820-8 PMID: 8113414
  72. Deregulated expression of the c-myc oncogene abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon-gamma, heparin, and cyclic nucleotide analogues and induces apoptosis.
    Circ Res. 1994 Mar;74(3):525-36 PMID: 8118960
  73. Signal transduction pathways involving the Raf proto-oncogene.
    Cancer Metastasis Rev. 1994 Mar;13(1):105-16 PMID: 8143342
  74. The Ras signal transduction pathway.
    Cancer Metastasis Rev. 1994 Mar;13(1):67-89 PMID: 8143346
  75. Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death.
    Curr Opin Genet Dev. 1994 Feb;4(1):102-8 PMID: 8193530
  76. Ternary complex factors: growth factor regulated transcriptional activators.
    Curr Opin Genet Dev. 1994 Feb;4(1):96-101 PMID: 8193547
  77. Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signaling.
    EMBO J. 1993 Nov;12(11):4181-9 PMID: 8223433
  78. The myc family of oncogenes and their presence and importance in small-cell lung carcinoma and other tumour types.
    Anticancer Res. 1993 Sep-Oct;13(5A):1373-85 PMID: 8239508
  79. Dual control of myc expression through a single DNA binding site targeted by ets family proteins and E2F-1.
    Oncogene. 1994 Feb;9(2):405-15 PMID: 8290253
  80. Site-specific modulation of c-Myc cotransformation by residues phosphorylated in vivo.
    Oncogene. 1994 Jan;9(1):59-70 PMID: 8302604
  81. Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro.
    Nature. 1993 Jul 22;364(6435):352-5 PMID: 8332195
  82. Mammalian Ras interacts directly with the serine/threonine kinase Raf.
    Cell. 1993 Jul 16;74(1):205-14 PMID: 8334704
  83. The c-myc oncogene in tumor progression.
    Crit Rev Oncog. 1993;4(4):435-49 PMID: 8353142
  84. The Src family tyrosine kinases are required for platelet-derived growth factor-mediated signal transduction in NIH 3T3 cells.
    Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7696-700 PMID: 8356071
  85. The ornithine decarboxylase gene is a transcriptional target of c-Myc.
    Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7804-8 PMID: 8356088
  86. The MAP kinase cascade is essential for diverse signal transduction pathways.
    Trends Biochem Sci. 1993 Apr;18(4):128-31 PMID: 8388132
  87. A dominant-negative mutant of raf blocks mitogen-activated protein kinase activation by growth factors and oncogenic p21ras.
    J Biol Chem. 1993 Sep 25;268(27):20232-6 PMID: 8397201
  88. Lysophosphatidic acid stimulates mitogen-activated protein kinase activation via a G-protein-coupled pathway requiring p21ras and p74raf-1.
    J Biol Chem. 1993 Oct 5;268(28):20717-20 PMID: 8407893
  89. Conditional transformation of cells and rapid activation of the mitogen-activated protein kinase cascade by an estradiol-dependent human raf-1 protein kinase.
    Mol Cell Biol. 1993 Oct;13(10):6241-52 PMID: 8413224
  90. Control of cell fate determination by p21ras/Ras1, an essential component of torso signaling in Drosophila.
    Genes Dev. 1993 Apr;7(4):621-32 PMID: 8458578
  91. Altered growth of human colon cancer cell lines disrupted at activated Ki-ras.
    Science. 1993 Apr 2;260(5104):85-8 PMID: 8465203
  92. C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation.
    Nature. 1993 May 13;363(6425):133-40 PMID: 8483497
  93. A branched signaling pathway for nerve growth factor is revealed by Src-, Ras-, and Raf-mediated gene inductions.
    Mol Cell Biol. 1993 Jun;13(6):3146-55 PMID: 8497245
  94. Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2.
    Mol Cell Biol. 1996 Feb;16(2):538-47 PMID: 8552081
  95. Antitumor effect of c-myc antisense phosphorothioate oligodeoxynucleotides on human melanoma cells in vitro and and in mice.
    J Natl Cancer Inst. 1996 Apr 3;88(7):419-29 PMID: 8618233
  96. Mammalian G1 cyclins and cell cycle progression.
    Proc Assoc Am Physicians. 1995 Jul;107(2):181-6 PMID: 8624851
  97. The transactivation potential of a c-Myc N-terminal region (residues 92-143) is regulated by growth factor/Ras signaling.
    Nucleic Acids Res. 1996 May 15;24(10):1971-8 PMID: 8657582
  98. Characterization of cell-specific modulatory element in the murine ornithine decarboxylase promoter.
    Biochem J. 1996 Jun 15;316 ( Pt 3):993-8 PMID: 8670180
  99. Regulation of cell-cell contacts in developing Drosophila eyes by Dsrc41, a new, close relative of vertebrate c-src.
    Genes Dev. 1996 Jul 1;10(13):1645-56 PMID: 8682295
  100. Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway.
    J Biol Chem. 1996 Aug 23;271(34):20608-16 PMID: 8702807
  101. Basic fibroblast growth factor selectively regulates ornithine decarboxylase gene expression in malignant H-ras transformed cells.
    J Cell Biochem. 1996 Mar 15;60(4):572-83 PMID: 8707896
  102. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer.
    Adv Cancer Res. 1996;68:67-108 PMID: 8712071
  103. Integration of growth factor signals at the c-fos serum response element.
    Philos Trans R Soc Lond B Biol Sci. 1996 Apr 29;351(1339):551-9 PMID: 8735278
  104. Roles of the MAP kinase cascade in vertebrates.
    Adv Pharmacol. 1996;36:121-37 PMID: 8783557
  105. Regulation of transcription by MAP kinase cascades.
    Curr Opin Cell Biol. 1996 Apr;8(2):205-15 PMID: 8791420
  106. Tumor inhibitory activity of anti-ras ribozymes delivered by retroviral gene transfer.
    Cancer Gene Ther. 1996 Jul-Aug;3(4):221-9 PMID: 8853546
  107. The cytokine-activated tyrosine kinase JAK2 activates Raf-1 in a p21ras-dependent manner.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11681-6 PMID: 8876196
  108. Apoptosis regulation by Raf, Bcl-2, and R-Ras.
    Recent Results Cancer Res. 1997;143:245-9 PMID: 8912424
  109. Regulation of cell cycle entry and G1 progression by CSF-1.
    Mol Reprod Dev. 1997 Jan;46(1):11-8 PMID: 8981358
  110. Cell cycle: on target with Myc.
    Curr Biol. 1996 Dec 1;6(12):1553-6 PMID: 8994810
  111. Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic ras and tyrosine kinases.
    J Biol Chem. 1997 Feb 14;272(7):4378-83 PMID: 9020159
  112. Signal transduction from multiple Ras effectors.
    Curr Opin Genet Dev. 1997 Feb;7(1):75-9 PMID: 9024640
  113. Mitogen-activated protein kinase pathways.
    Curr Opin Cell Biol. 1997 Apr;9(2):180-6 PMID: 9069255
  114. Src family protein tyrosine kinases: cooperating with growth factor and adhesion signaling pathways.
    Curr Opin Cell Biol. 1997 Apr;9(2):187-92 PMID: 9069259
  115. The complexity of Raf-1 regulation.
    Curr Opin Cell Biol. 1997 Apr;9(2):174-9 PMID: 9069260
  116. Elimination of cyclin D1 in vertebrate cells leads to an altered cell cycle phenotype, which is rescued by overexpression of murine cyclins D1, D2, or D3 but not by a mutant cyclin D1.
    J Biol Chem. 1997 Apr 18;272(16):10859-69 PMID: 9099742
  117. Rapid phosphorylation of Ets-2 accompanies mitogen-activated protein kinase activation and the induction of heparin-binding epidermal growth factor gene expression by oncogenic Raf-1.
    Mol Cell Biol. 1997 May;17(5):2401-12 PMID: 9111309
  118. The Raf/MAP kinase cascade in cell cycle regulation and differentiation in Drosophila.
    Cell Struct Funct. 1996 Oct;21(5):437-44 PMID: 9118253
  119. Induction of c-myc transcription by the v-Abl tyrosine kinase requires Ras, Raf1, and cyclin-dependent kinases.
    Genes Dev. 1997 Mar 1;11(5):654-62 PMID: 9119229
  120. Cell cycle: routine role for Ras.
    Curr Biol. 1997 Apr 1;7(4):R258-60 PMID: 9162506
  121. Defining a role for c-Myc in breast tumorigenesis.
    Breast Cancer Res Treat. 1997 May;44(1):1-22 PMID: 9164674
  122. Activation of c-Raf-1 by Ras and Src through different mechanisms: activation in vivo and in vitro.
    EMBO J. 1997 May 1;16(9):2384-96 PMID: 9171352
  123. Myc target genes.
    Trends Biochem Sci. 1997 May;22(5):177-81 PMID: 9175477
  124. Effects of phosphodiester and phosphorothioate antisense oligodeoxynucleotides on cell lines which overexpress c-myc: implications for the treatment of Burkitt's lymphoma.
    Ann Oncol. 1997;8 Suppl 1:25-30 PMID: 9187425
  125. Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1.
    Mol Cell Biol. 1997 Sep;17(9):5598-611 PMID: 9271435
  126. Identification of immediate-early gene targets of the Raf-1 serine/threonine protein kinase using an estradiol-dependent fusion protein, delta Raf-1:ER.
    Methods Mol Biol. 1997;85:137-51 PMID: 9276321
  127. Mutations of critical amino acids affect the biological and biochemical properties of oncogenic A-Raf and Raf-1.
    Oncogene. 1997 Aug 28;15(9):1021-33 PMID: 9285556
  128. Analysis of ornithine decarboxylase messenger ribonucleic acid expression in colorectal carcinoma.
    Dis Colon Rectum. 1997 Sep;40(9):1095-100 PMID: 9293942
  129. Induction of ornithine decarboxylase by IL-3 is mediated by sequential c-Myc-independent and c-Myc-dependent pathways.
    Oncogene. 1997 Sep 4;15(10):1219-32 PMID: 9294616
  130. Ras effectors and their role in mitogenesis and oncogenesis.
    J Mol Med (Berl). 1997 Aug;75(8):587-93 PMID: 9297626
  131. The role of c-myc during normal B cell proliferation, and as B cells undergo malignant transformation.
    Curr Top Microbiol Immunol. 1997;224:211-20 PMID: 9308244
  132. K-ras is an essential gene in the mouse with partial functional overlap with N-ras.
    Genes Dev. 1997 Oct 1;11(19):2468-81 PMID: 9334313
  133. Cellular functions regulated by Src family kinases.
    Annu Rev Cell Dev Biol. 1997;13:513-609 PMID: 9442882
  134. Regulation of c-myc expression by Ras/Raf signalling.
    Oncogene. 1998 Jan 15;16(2):211-6 PMID: 9464539
  135. Activation of SRF-regulated chromosomal templates by Rho-family GTPases requires a signal that also induces H4 hyperacetylation.
    Cell. 1998 Feb 20;92(4):475-87 PMID: 9491889
  136. Ets-2 transdominant mutant abolishes anchorage-independent growth and macrophage colony-stimulating factor-stimulated invasion by BT20 breast carcinoma cells.
    Cancer Res. 1998 Mar 1;58(5):1027-33 PMID: 9500466
  137. Persistent activation of mitogen-activated protein kinases p42 and p44 and ets-2 phosphorylation in response to colony-stimulating factor 1/c-fms signaling.
    Mol Cell Biol. 1998 Sep;18(9):5148-56 PMID: 9710599
  138. The repertoire of fos and jun proteins expressed during the G1 phase of the cell cycle is determined by the duration of mitogen-activated protein kinase activation.
    Mol Cell Biol. 1999 Jan;19(1):330-41 PMID: 9858557
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.2.1101
Published
1999-02-00
Pages
1101-15
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC116040
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.19.2.1101 PMC Full Text View journal details
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