Experimental Hematology
Volume 30, Issue 10 , Pages 1089-1106 , October 2002

Ras and relatives—job sharing and networking keep an old family together

  • Annette Ehrhardt

      Affiliations

    • The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Götz R.A Ehrhardt

      Affiliations

    • Comprehensive Cancer Centre, University of Alabama, Birmingham, Ala., USA
  • ,
  • Xuecui Guo

      Affiliations

    • The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • John W Schrader

      Affiliations

    • Corresponding Author InformationOffprint requests to: John W. Schrader, M.B., Ph.D., The Biomedical Research Centre, University of British Columbia, Vancouver V6T 1Z3, Canada
    • The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

References 

  1. Harvey JJ. An unidentified virus which causes the rapid production of tumours in mice. Nature. 1964;204:1104
  2. Kirsten WH, Mayer LA. Morphologic responses to a murine erythroblastosis virus. J Natl Cancer Inst. 1967;39:311
  3. Lenzen C, Cool RH, Prinz H, Kuhlmann J, Wittinghofer A. Kinetic analysis by fluorescence of the interaction between Ras and the catalytic domain of the guanine nucleotide exchange factor Cdc25Mm. Biochemistry. 1998;37:7420
  4. Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J. The structural basis of the activation of Ras by Sos. Nature. 1998;394:337
  5. Reuther GW, Der CJ. The Ras branch of small GTPases (Ras family members don't fall far from the tree). Curr Opin Cell Biol. 2000;12:157
  6. Casey PJ. Protein lipidation in cell signaling. Science. 1995;268:221
  7. Reuter CW, Morgan MA, Bergmann L. Targeting the Ras signaling pathway (a rational, mechanism-based treatment for hematologic malignancies?). Blood. 2000;96:1655
  8. Hancock JF, Paterson H, Marshall CJ. A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane. Cell. 1990;63:133
  9. Hancock JF, Magee AI, Childs JE, Marshall CJ. All ras proteins are polyisoprenylated but only some are palmitoylated. Cell. 1989;57:1167
  10. Choy E, Chiu VK, Silletti J, et al.  Endomembrane trafficking of ras (the CAAX motif targets proteins to the ER and Golgi). Cell. 1999;98:69
  11. Apolloni A, Prior IA, Lindsay M, Parton RG, Hancock JF. H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway. Mol Cell Biol. 2000;20:2475
  12. Thissen JA, Gross JM, Subramanian K, Meyer T, Casey PJ. Prenylation-dependent association of Ki-Ras with microtubules. Evidence for a role in subcellular trafficking. J Biol Chem. 1997;272:30362
  13. Roy S, Luetterforst R, Harding A, et al.  Dominant-negative caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains. Nat Cell Biol. 1999;1:98
  14. Prior IA, Harding A, Yan J, et al.  GTP-dependent segregation of H-ras from lipid rafts is required for biological activity. Nat Cell Biol. 2001;3:368
  15. Jaumot M, Yan J, Clyde-Smith J, Sluimer J, Hancock JF. The linker domain of the H-Ras hypervariable region regulates interactions with exchange factors, Raf-1 and phosphoinositide 3-kinase. J Biol Chem. 2001;31:31
  16. Cheng PC, Brown BK, Song W, Pierce SK. Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling. J Immunol. 2001;166:3693
  17. Xavier R, Brennan T, Li Q, McCormack C, Seed B. Membrane compartmentation is required for efficient T cell activation. Immunity. 1998;8:723
  18. Sheets ED, Holowka D, Baird B. Critical role for cholesterol in Lyn-mediated tyrosine phosphorylation of FcepsilonRI and their association with detergent-resistant membranes. J Cell Biol. 1999;145:877
  19. Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000;1:31
  20. Lisanti MP, Scherer PE, Vidugiriene J, et al.  Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source (implications for human disease). J Cell Biol. 1994;126:111
  21. Wei W, Mosteller RD, Sanyal P, et al.  Identification of a mammalian gene structurally and functionally related to the CDC25 gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1992;89:7100
  22. Cen H, Papageorge AG, Zippel R, Lowy DR, Zhang K. Isolation of multiple mouse cDNAs with coding homology to Saccharomyces cerevisiae CDC25 (identification of a region related to Bcr, Vav, Dbl and CDC24). Embo J. 1992;11:4007
  23. Martegani E, Vanoni M, Zippel R, et al.  Cloning by functional complementation of a mouse cDNA encoding a homologue of CDC25, a Saccharomyces cerevisiae RAS activator. Embo J. 1992;11:2151
  24. Fam NP, Fan WT, Wang Z, et al.  Cloning and characterization of Ras-GRF2, a novel guanine nucleotide exchange factor for Ras. Mol Cell Biol. 1997;17:1396
  25. Jones MK, Jackson JH. Ras-GRF activates Ha-Ras, but not N-Ras or K-Ras 4B, protein in vivo. J Biol Chem. 1998;273:1782
  26. Ohba Y, Mochizuki N, Yamashita S, et al.  Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3. J Biol Chem. 2000;275:20020
  27. Gotoh T, Tian X, Feig LA. Prenylation of target gtpases contributes to signaling specificity of ras-guanine nucleotide exchange factors. J Biol Chem. 2001;276:38029
  28. de Hoog CL, Fan WT, Goldstein MD, Moran MF, Koch CA. Calmodulin-independent coordination of Ras and extracellular signal-regulated kinase activation by Ras-GRF2. Mol Cell Biol. 2000;20:2727
  29. Bowtell D, Fu P, Simon M, Senior P. Identification of murine homologues of the Drosophila son of sevenless gene (potential activators of ras). Proc Natl Acad Sci U S A. 1992;89:6511
  30. Chardin P, Camonis JH, Gale NW, et al.  Human Sos1 (a guanine nucleotide exchange factor for Ras that binds to GRB2). Science. 1993;260:1338
  31. Nielsen KH, Gredsted L, Broach JR, Willumsen BM. Sensitivity of wild type and mutant ras alleles to Ras specific exchange factors (Identification of factor specific requirements). Oncogene. 2001;20:2091
  32. Liu BX, Wei W, Broek D. The catalytic domain of the mouse sos1 gene product activates Ras proteins in vivo and in vitro. Oncogene. 1993;8:3081
  33. Tognon CE, Kirk HE, Passmore LA, et al.  Regulation of RasGRP via a phorbol ester-responsive C1 domain. Mol Cell Biol. 1998;18:6995
  34. Clyde-Smith J, Silins G, Gartside M, et al.  Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor. J Biol Chem. 2000;275:32260
  35. Yamashita S, Mochizuki N, Ohba Y, et al.  CalDAG-GEFIII activation of Ras, R-ras, and Rap1. J Biol Chem. 2000;275:25488
  36. Kawasaki H, Springett GM, Toki S, et al.  A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc Natl Acad Sci U S A. 1998;95:13278
  37. Lorenzo PS, Kung JW, Bottorff DA, et al.  Phorbol esters modulate the Ras exchange factor RasGRP3. Cancer Res. 2001;61:943
  38. Yang Y, Li L, Wong GW, et al.  RasGRP4, a new mast cell-restricted ras guanine nucleotide releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients; and demonstration of the importance of RasGRP4 in mast cell development and function. J Biol Chem. 2002;15:15
  39. Reuther GW, Lambert QT, Rebhun JF, et al.  RasGRP4 is a novel ras activator isolated from acute myeloid leukemia. J Biol Chem. 2002;5:5
  40. Kawasaki H, Springett GM, Mochizuki N, et al.  A family of cAMP-binding proteins that directly activate Rap1. Science. 1998;282:2275
  41. Rebhun JF, Castro AF, Quilliam LA. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. J Biol Chem. 2000;275:34901
  42. Gao X, Satoh T, Liao Y, et al.  Identification and characterization of RA-GEF-2, a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras. J Biol Chem. 2001;276:42219
  43. Jin TG, Satoh T, Liao Y, et al.  Role of the CDC25 homology domain of phospholipase Cepsilon in amplification of Rap1-dependent signaling. J Biol Chem. 2001;276:30301
  44. Gotoh T, Cai D, Tian X, Feig LA, Lerner A. p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor. J Biol Chem. 2000;275:30118
  45. Tanaka S, Morishita T, Hashimoto Y, et al.  C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins. Proc Natl Acad Sci U S A. 1994;91:3443
  46. Chiang SH, Baumann CA, Kanzaki M, et al.  Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature. 2001;410:944
  47. Kaibuchi K, Mizuno T, Fujioka H, et al.  Molecular cloning of the cDNA for stimulatory GDP/GTP exchange protein for smg p21s (ras p21-like small GTP-binding proteins) and characterization of stimulatory GDP/GTP exchange protein. Mol Cell Biol. 1991;11:2873
  48. Takai Y, Kaibuchi K, Kikuchi A, Sasaki T, Shirataki H. Regulators of small GTPases. Ciba Found Symp. 1993;176:128
  49. Vikis HG, Stewart S, Guan KL. SmgGDS displays differential binding and exchange activity towards different Ras isoforms. Oncogene. 2002;21:2425
  50. Tian X, Feig LA. Basis for Signaling Specificity Difference between Sos and Ras-GRF Guanine Nucleotide Exchange Factors. J Biol Chem. 2001;276:47248
  51. Ahmadian MR, Stege P, Scheffzek K, Wittinghofer A. Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras. Nat Struct Biol. 1997;4:686
  52. Adari H, Lowy DR, Willumsen BM, Der CJ, McCormick F. Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain. Science. 1988;240:518
  53. Martin GA, Yatani A, Clark R, et al.  GAP domains responsible for ras p21-dependent inhibition of muscarinic atrial K+ channel currents. Science. 1992;255:192
  54. Medema RH, de Laat WL, Martin GA, McCormick F, Bos JL. GTPase-activating protein SH2-SH3 domains induce gene expression in a Ras-dependent fashion. Mol Cell Biol. 1992;12:3425
  55. Ellis C, Moran M, McCormick F, Pawson T. Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases. Nature. 1990;343:377
  56. Settleman J, Albright CF, Foster LC, Weinberg RA. Association between GTPase activators for Rho and Ras families. Nature. 1992;359:153
  57. McGlade J, Brunkhorst B, Anderson D, et al.  The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion. Embo J. 1993;12:3073
  58. Druker B, Okuda K, Matulonis U, et al.  Tyrosine phosphorylation of rasGAP and associated proteins in chronic myelogenous leukemia cell lines. Blood. 1992;79:2215
  59. Amrein KE, Flint N, Panholzer B, Burn P. Ras GTPase-activating protein (a substrate and a potential binding protein of the protein-tyrosine kinase p56lck). Proc Natl Acad Sci U S A. 1992;89:3343
  60. Xu GF, O'Connell P, Viskochil D, et al.  The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell. 1990;62:599
  61. Maekawa M, Li S, Iwamatsu A, et al.  A novel mammalian Ras GTPase-activating protein which has phospholipid-binding and Btk homology regions. Mol Cell Biol. 1994;14:6879
  62. Yamamoto T, Matsui T, Nakafuku M, Iwamatsu A, Kaibuchi K. A novel GTPase-activating protein for R-Ras. J Biol Chem. 1995;270:30557
  63. Baba H, Fuss B, Urano J, et al.  GapIII, a new brain-enriched member of the GTPase-activating protein family. J Neurosci Res. 1995;41:846
  64. Wittinghofer A. Signal transduction via Ras. Biol Chem. 1998;379:933
  65. Jiang Y, Ma W, Wan Y, et al.  The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain. Nature. 1998;395:808
  66. Albright CF, Giddings BW, Liu J, Vito M, Weinberg RA. Characterization of a guanine nucleotide dissociation stimulator for a ras-related GTPase. Embo J. 1993;12:339
  67. Spaargaren M, Bischoff JR. Identification of the guanine nucleotide dissociation stimulator for Ral as a putative effector molecule of R-ras, H-ras, K-ras, and Rap. Proc Natl Acad Sci U S A. 1994;91:12609
  68. Kikuchi A, Demo SD, Ye ZH, Chen YW, Williams LT. ralGDS family members interact with the effector loop of ras p21. Mol Cell Biol. 1994;14:7483
  69. Wolthuis RM, Bauer B, van't Veer LJ, et al.  RalGDS-like factor (Rlf) is a novel Ras and Rap 1A-associating protein. Oncogene. 1996;13:353
  70. Shao H, Andres DA. A novel RalGEF-like protein, RGL3, as a candidate effector for rit and Ras. J Biol Chem. 2000;275:26914
  71. Ehrhardt GR, Korherr C, Wieler JS, Knaus M, Schrader JW. A novel potential effector of M-Ras and p21 Ras negatively regulates p21 Ras-mediated gene induction and cell growth. Oncogene. 2001;20:188
  72. Rebhun JF, Chen H, Quilliam LA. Identification and characterization of a new family of guanine nucleotide exchange factors for the ras-related GTPase Ral. J Biol Chem. 2000;275:13406
  73. de Bruyn KM, de Rooij J, Wolthuis RM, et al.  RalGEF2, a pleckstrin homology domain containing guanine nucleotide exchange factor for Ral. J Biol Chem. 2000;275:29761
  74. D'Adamo DR, Novick S, Kahn JM, Leonardi P, Pellicer A. rsc (a novel oncogene with structural and functional homology with the gene family of exchange factors for Ral). Oncogene. 1997;14:1295
  75. Rosario M, Paterson HF, Marshall CJ. Activation of the Ral and phosphatidylinositol 3[prime] kinase signaling pathways by the ras-related protein TC21. Mol Cell Biol. 2001;21:3750
  76. Murphy GA, Graham SM, Morita S, et al.  Involvement of phosphatidylinositol 3-kinase, but not RalGDS, in TC21/R-Ras2-mediated transformation. J Biol Chem. 2002;11:11
  77. Hofer F, Fields S, Schneider C, Martin GS. Activated Ras interacts with the Ral guanine nucleotide dissociation stimulator. Proc Natl Acad Sci U S A. 1994;91:11089
  78. Kelley GG, Reks SE, Ondrako JM, Smrcka AV. Phospholipase C(epsilon) (a novel Ras effector). Embo J. 2001;20:743
  79. Han L, Colicelli J. A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1. Mol Cell Biol. 1995;15:1318
  80. Tall GG, Barbieri MA, Stahl PD, Horazdovsky BF. Ras-activated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1. Dev Cell. 2001;1:73
  81. Vojtek AB, Hollenberg SM, Cooper JA. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell. 1993;74:205
  82. Zhang XF, Settleman J, Kyriakis JM, et al.  Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1. Nature. 1993;364:308
  83. Rizzo MA, Shome K, Watkins SC, Romero G. The recruitment of Raf-1 to membranes is mediated by direct interaction with phosphatidic acid and is independent of association with Ras. J Biol Chem. 2000;275:23911
  84. Voice JK, Klemke RL, Le A, Jackson JH. Four human ras homologs differ in their abilities to activate Raf-1, induce transformation, and stimulate cell motility. J Biol Chem. 1999;274:17164
  85. Marte BM, Rodriguez-Viciana P, Wennstrom S, Warne PH, Downward J. R-Ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of the Ras effector pathways. Curr Biol. 1997;7:63
  86. Kimmelman A, Tolkacheva T, Lorenzi MV, Osada M, Chan AM. Identification and characterization of R-ras3 (a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution). Oncogene. 1997;15:2675
  87. Quilliam LA, Castro AF, Rogers-Graham KS, et al.  M-Ras/ R-Ras3, a transforming ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6. J Biol Chem. 1999;274:23850
  88. Rosario M, Paterson HF, Marshall CJ. Activation of the Raf/MAP kinase cascade by the Ras-related protein TC21 is required for the TC21-mediated transformation of NIH 3T3 cells. Embo J. 1999;18:1270
  89. Graham SM, Vojtek AB, Huff SY, et al.  TC21 causes transformation by Raf-independent signaling pathways. Mol Cell Biol. 1996;16:6132
  90. Movilla N, Crespo P, Bustelo XR. Signal transduction elements of TC21, an oncogenic member of the R-Ras subfamily of GTP-binding proteins. Oncogene. 1999;18:5860
  91. Graham SM, Cox AD, Drivas G, et al.  Aberrant function of the Ras-related protein TC21/R-Ras2 triggers malignant transformation. Mol Cell Biol. 1994;14:4108
  92. York RD, Yao H, Dillon T, et al.  Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature. 1998;392:622
  93. Lange-Carter CA, Pleiman CM, Gardner AM, Blumer KJ, Johnson GL. A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science. 1993;260:315
  94. Xu S, Robbins DJ, Christerson LB, et al.  Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane–associated 195-kDa protein with a large regulatory domain. Proc Natl Acad Sci U S A. 1996;93:5291
  95. Lange-Carter CA, Johnson GL. Ras-dependent growth factor regulation of MEK kinase in PC12 cells. Science. 1994;265:1458
  96. Russell M, Lange-Carter CA, Johnson GL. Direct interaction between Ras and the kinase domain of mitogen- activated protein kinase kinase kinase (MEKK1). J Biol Chem. 1995;270:11757
  97. Lee FS, Peters RT, Dang LC, Maniatis T. MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. Proc Natl Acad Sci U S A. 1998;95:9319
  98. Rodriguez-Viciana P, Warne PH, Dhand R, et al.  Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature. 1994;370:527
  99. Katso R, Okkenhaug K, Ahmadi K, et al.  Cellular function of phosphoinositide 3-kinases (implications for development, homeostasis, and cancer). Annu Rev Cell Dev Biol. 2001;17:615
  100. Yan J, Roy S, Apolloni A, Lane A, Hancock JF. Ras isoforms vary in their ability to activate Raf-1 and phosphoinositide 3-kinase. J Biol Chem. 1998;273:24052
  101. Kimmelman AC, Osada M, Chan AM. R-Ras3, a brain-specific Ras-related protein, activates Akt and promotes cell survival in PC12 cells. Oncogene. 2000;19:2014
  102. Satoh T, Nakafuku M, Miyajima A, Kaziro Y. Involvement of ras p21 protein in signal-transduction pathways from interleukin 2, interleukin 3, and granulocyte/macrophage colony-stimulating factor, but not from interleukin 4. Proc Natl Acad Sci U S A. 1991;88:3314
  103. Welham MJ, Bone H, Levings M, et al.  Insulin receptor substrate-2 is the major 170-kDa protein phosphorylated on tyrosine in response to cytokines in murine lymphohemopoietic cells. J Biol Chem. 1997;272:1377
  104. Nimnual AS, Yatsula BA, Bar-Sagi D. Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos. Science. 1998;279:560
  105. Han J, Luby-Phelps K, Das B, et al.  Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science. 1998;279:558
  106. Michiels F, Stam JC, Hordijk PL, et al.  Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and C-Jun NH2-terminal kinase activation. J Cell Biol. 1997;137:387
  107. Walsh AB, Bar-Sagi D. Differential activation of the Rac pathway by Ha-Ras and K-Ras. J Biol Chem. 2001;276:15609
  108. Diaz-Meco MT, Lozano J, Municio MM, et al.  Evidence for the in vitro and in vivo interaction of Ras with protein kinase C zeta. J Biol Chem. 1994;269:31706
  109. Uberall F, Hellbert K, Kampfer S, et al.  Evidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeleton. J Cell Biol. 1999;144:413
  110. Kampfer S, Windegger M, Hochholdinger F, et al.  Protein kinase C isoforms involved in the transcriptional activation of cyclin D1 by transforming Ha-Ras. J Biol Chem. 2001;276:42834
  111. Wang Y, Waldron RT, Dhaka A, et al.  The RAS effector RIN1 directly competes with RAF and is regulated by 14- 3-3 proteins. Mol Cell Biol. 2002;22:916
  112. Vavvas D, Li X, Avruch J, Zhang XF. Identification of Nore1 as a potential Ras effector. J Biol Chem. 1998;273:5439
  113. Ortiz-Vega S, Khokhlatchev A, Nedwidek M, et al.  The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1. Oncogene. 2002;21:1381
  114. Khokhlatchev A, Rabizadeh S, Xavier R, et al.  Identification of a novel ras-regulated proapoptotic pathway. Curr Biol. 2002;12:253
  115. Vos MD, Ellis CA, Bell A, Birrer MJ, Clark GJ. Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. J Biol Chem. 2000;275:35669
  116. Matsuo T, Takahashi K, Suzuki E, Yamamoto D. The Canoe protein is necessary in adherens junctions for development of ommatidial architecture in the Drosophila compound eye. Cell Tissue Res. 1999;298:397
  117. Boettner B, Govek EE, Cross J, Van Aelst L. The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin. Proc Natl Acad Sci U S A. 2000;97:9064
  118. Villalonga P, Lopez-Alcala C, Bosch M, et al.  Calmodulin binds to K-Ras, but not to H- or N-Ras, and modulates its downstream signaling. Mol Cell Biol. 2001;21:7345
  119. Ehrhardt GR, Leslie KB, Lee F, Wieler JS, Schrader JW. M-Ras, a widely expressed 29-kD homologue of p21 Ras (expression of a constitutively active mutant results in factor-independent growth of an interleukin-3–dependent cell line). Blood. 1999;94:2433
  120. Feig LA. Tools of the trade (use of dominant-inhibitory mutants of Ras-family GTPases). Nat Cell Biol. 1999;1:E25
  121. Mulcahy LS, Smith MR, Stacey DW. Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells. Nature. 1985;313:241
  122. Duronio V, Welham MJ, Abraham S, Dryden P, Schrader JW. p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein. Proc Natl Acad Sci U S A. 1992;89:1587
  123. Satoh T, Endo M, Nakafuku M, et al.  Accumulation of p21ras. GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity. Proc Natl Acad Sci U S A. 1990;87:7926
  124. Satoh T, Endo M, Nakafuku M, Nakamura S, Kaziro Y. Platelet-derived growth factor stimulates formation of active p21ras.GTP complex in Swiss mouse 3T3 cells. Proc Natl Acad Sci U S A. 1990;87:5993
  125. Taylor SJ, Shalloway D. Cell cycle–dependent activation of Ras. Curr Biol. 1996;6:1621
  126. Swan KA, Alberola-Ila J, Gross JA, et al.  Involvement of p21ras distinguishes positive and negative selection in thymocytes. Embo J. 1995;14:276
  127. Iritani BM, Forbush KA, Farrar MA, Perlmutter RM. Control of B cell development by Ras-mediated activation of Raf. Embo J. 1997;16:7019
  128. Umanoff H, Edelmann W, Pellicer A, Kucherlapati R. The murine N-ras gene is not essential for growth and development. Proc Natl Acad Sci U S A. 1995;92:1709
  129. Esteban LM, Vicario-Abejon C, Fernandez-Salguero P, et al.  Targeted genomic disruption of H-ras and N-ras, individually or in combination, reveals the dispensability of both loci for mouse growth and development. Mol Cell Biol. 2001;21:1444
  130. Wolfman JC, Wolfman A. Endogenous c-N-Ras provides a steady-state anti-apoptotic signal. J Biol Chem. 2000;275:19315
  131. Johnson L, Greenbaum D, Cichowski K, et al.  K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes Dev. 1997;11:2468
  132. Koera K, Nakamura K, Nakao K, et al.  K-ras is essential for the development of the mouse embryo. Oncogene. 1997;15:1151
  133. Pells S, Divjak M, Romanowski P, et al.  Developmentally regulated expression of murine K-ras isoforms. Oncogene. 1997;15:1781
  134. Hariharan IK, Carthew RW, Rubin GM. The Drosophila roughened mutation (activation of a rap homolog disrupts eye development and interferes with cell determination). Cell. 1991;67:717
  135. Asha H, de Ruiter ND, Wang MG, Hariharan IK. The Rap1 GTPase functions as a regulator of morphogenesis in vivo. Embo J. 1999;18:605
  136. Sawamoto K, Winge P, Koyama S, et al.  The Drosophila Ral GTPase regulates developmental cell shape changes through the Jun NH(2)-terminal kinase pathway. J Cell Biol. 1999;146:361
  137. Feig LA, Cooper GM. Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP. Mol Cell Biol. 1988;8:3235
  138. Dobrowolski S, Harter M, Stacey DW. Cellular ras activity is required for passage through multiple points of the G0/G1 phase in BALB/c 3T3 cells. Mol Cell Biol. 1994;14:5441
  139. Aktas H, Cai H, Cooper GM. Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1. Mol Cell Biol. 1997;17:3850
  140. Maher J, Baker DA, Manning M, Dibb NJ, Roberts IA. Evidence for cell-specific differences in transformation by N-, H- and K-ras. Oncogene. 1995;11:1639
  141. Crespo P, Leon J. Ras proteins in the control of the cell cycle and cell differentiation. Cell Mol Life Sci. 2000;57:1613
  142. Pruitt K, Der CJ. Ras and Rho regulation of the cell cycle and oncogenesis. Cancer Lett. 2001;171:1
  143. Sherr CJ. The INK4a/ARF network in tumour suppression. Nat Rev Mol Cell Biol. 2001;2:731
  144. Kamijo T, Zindy F, Roussel MF, et al.  Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell. 1997;91:649
  145. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997;88:593
  146. Woods D, Parry D, Cherwinski H, et al.  Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1. Mol Cell Biol. 1997;17:5598
  147. Sewing A, Wiseman B, Lloyd AC, Land H. High-intensity Raf signal causes cell cycle arrest mediated by p21Cip1. Mol Cell Biol. 1997;17:5588
  148. Delgado MD, Vaque JP, Arozarena I, et al.  H-, K- and N-Ras inhibit myeloid leukemia cell proliferation by a p21WAF1-dependent mechanism. Oncogene. 2000;19:783
  149. Schondorf T, Rutzel S, Andrack A, et al.  Immunohistochemical analysis reveals a protective effect of H-ras expression mediated via apoptosis in node-negative breast cancer patients. Int J Oncol. 2002;20:273
  150. Hughes PE, Renshaw MW, Pfaff M, et al.  Suppression of integrin activation (a novel function of a Ras/Raf- initiated MAP kinase pathway). Cell. 1997;88:521
  151. Shibayama H, Anzai N, Braun SE, et al.  H-Ras is involved in the inside-out signaling pathway of interleukin-3–induced integrin activation. Blood. 1999;93:1540
  152. Zhang Z, Vuori K, Wang H, Reed JC, Ruoslahti E. Integrin activation by R-ras. Cell. 1996;85:61
  153. Zou JX, Liu Y, Pasquale EB, Ruoslahti E. Activated SRC oncogene phosphorylates R-ras and suppresses integrin activity. J Biol Chem. 2002;277:1824
  154. Tsukamoto N, Hattori M, Yang H, Bos JL, Minato N. Rap1 GTPase-activating protein SPA-1 negatively regulates cell adhesion. J Biol Chem. 1999;274:18463
  155. Urano T, Emkey R, Feig LA. Ral-GTPases mediate a distinct downstream signaling pathway from Ras that facilitates cellular transformation. Embo J. 1996;15:810
  156. Cantor SB, Urano T, Feig LA. Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases. Mol Cell Biol. 1995;15:4578
  157. Quaroni A, Paul EC. Cytocentrin is a Ral-binding protein involved in the assembly and function of the mitotic apparatus. J Cell Sci. 1999;112:707
  158. Henry DO, Moskalenko SA, Kaur KJ, et al.  Ral GTPases contribute to regulation of cyclin D1 through activation of NF-kappaB. Mol Cell Biol. 2000;20:8084
  159. Jiang H, Luo JQ, Urano T, et al.  Involvement of Ral GTPase in v-Src-induced phospholipase D activation. Nature. 1995;378:409
  160. Luo JQ, Liu X, Frankel P, et al.  Functional association between Arf and RalA in active phospholipase D complex. Proc Natl Acad Sci U S A. 1998;95:3632
  161. Suzuki J, Yamazaki Y, Li G, Kaziro Y, Koide H. Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts. Mol Cell Biol. 2000;20:4658
  162. Nakashima S, Morinaka K, Koyama S, et al.  Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. Embo J. 1999;18:3629
  163. Goi T, Shipitsin M, Lu Z, et al.  An EGF receptor/Ral-GTPase signaling cascade regulates c-Src activity and substrate specificity. Embo J. 2000;19:623
  164. de Ruiter ND, Wolthuis RM, van Dam H, Burgering BM, Bos JL. Ras-dependent regulation of c-Jun phosphorylation is mediated by the Ral guanine nucleotide exchange factor-Ral pathway. Mol Cell Biol. 2000;20:8480
  165. Wolthuis RM, Franke B, van Triest M, et al.  Activation of the small GTPase Ral in platelets. Mol Cell Biol. 1998;18:2486
  166. Kitayama H, Matsuzaki T, Sugimoto Y, Ikawa Y, Noda M. Genetic analysis of the K-rev-1 transformation-suppressor gene. Environ Health Perspect. 1991;93:73
  167. Okada S, Matsuda M, Anafi M, Pawson T, Pessin JE. Insulin regulates the dynamic balance between Ras and Rap1 signaling by coordinating the assembly states of the Grb2-SOS and CrkII-C3G complexes. Embo J. 1998;17:2554
  168. Cook SJ, Rubinfeld B, Albert I, McCormick F. RapV12 antagonizes Ras-dependent activation of ERK1 and ERK2 by LPA and EGF in Rat-1 fibroblasts. Embo J. 1993;12:3475
  169. Zwartkruis FJ, Wolthuis RM, Nabben NM, Franke B, Bos JL. Extracellular signal-regulated activation of Rap1 fails to interfere in Ras effector signalling. Embo J. 1998;17:5905
  170. Ohba Y, Mochizuki N, Matsuo K, et al.  Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade. Mol Cell Biol. 2000;20:6074
  171. Alberola-Ila J, Forbush KA, Seger R, Krebs EG, Perlmutter RM. Selective requirement for MAP kinase activation in thymocyte differentiation. Nature. 1995;373:620
  172. Molina TJ, Kishihara K, Siderovski DP, et al.  Profound block in thymocyte development in mice lacking p56lck. Nature. 1992;357:161
  173. Pages G, Guerin S, Grall D, et al.  Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Science. 1999;286:1374
  174. Dower NA, Stang SL, Bottorff DA, et al.  RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nat Immunol. 2000;1:317
  175. Sharp LL, Schwarz DA, Bott CM, Marshall CJ, Hedrick SM. The influence of the MAPK pathway on T cell lineage commitment. Immunity. 1997;7:609
  176. Puente LG, Stone JC, Ostergaard HL. Evidence for protein kinase C-dependent and -independent activation of mitogen-activated protein kinase in T cells (potential role of additional diacylglycerol binding proteins). J Immunol. 2000;165:6865
  177. Yamashita M, Kimura M, Kubo M, et al.  T cell antigen receptor-mediated activation of the Ras/mitogen-activated protein kinase pathway controls interleukin 4 receptor function and type-2 helper T cell differentiation. Proc Natl Acad Sci U S A. 1999;96:1024
  178. Downward J, Graves JD, Warne PH, Rayter S, Cantrell DA. Stimulation of p21ras upon T-cell activation. Nature. 1990;346:719
  179. Izquierdo M, Downward J, Graves JD, Cantrell DA. Role of protein kinase C in T-cell antigen receptor regulation of p21ras (evidence that two p21ras regulatory pathways coexist in T cells). Mol Cell Biol. 1992;12:3305
  180. Ebinu JO, Bottorff DA, Chan EY, et al.  RasGRP, a Ras guanyl nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Science. 1998;280:1082
  181. Altman A, Deckert M. The function of small GTPases in signaling by immune recognition and other leukocyte receptors. Adv Immunol. 1999;72:1
  182. Reedquist KA, Bos JL. Costimulation through CD28 suppresses T cell receptor-dependent activation of the Ras-like small GTPase Rap1 in human T lymphocytes. J Biol Chem. 1998;273:4944
  183. Fields PE, Gajewski TF, Fitch FW. Blocked Ras activation in anergic CD4+ T cells. Science. 1996;271:1276
  184. Boussiotis VA, Freeman GJ, Berezovskaya A, Barber DL, Nadler LM. Maintenance of human T cell anergy (blocking of IL-2 gene transcription by activated Rap1). Science. 1997;278:124
  185. Nagaoka H, Takahashi Y, Hayashi R, et al.  Ras mediates effector pathways responsible for pre-B cell survival, which is essential for the developmental progression to the late pre-B cell stage. J Exp Med. 2000;192:171
  186. Shaw AC, Swat W, Ferrini R, Davidson L, Alt FW. Activated Ras signals developmental progression of recombinase-activating gene (RAG)-deficient pro-B lymphocytes. J Exp Med. 1999;189:123
  187. Harwood AE, Cambier JC. B cell antigen receptor cross-linking triggers rapid protein kinase C independent activation of p21ras1. J Immunol. 1993;151:4513
  188. Saxton TM, van Oostveen I, Bowtell D, Aebersold R, Gold MR. B cell antigen receptor cross-linking induces phosphorylation of the p21ras oncoprotein activators SHC and mSOS1 as well as assembly of complexes containing SHC, GRB-2, mSOS1, and a 145-kDa tyrosine- phosphorylated protein. J Immunol. 1994;153:623
  189. Graziadei L, Riabowol K, Bar-Sagi D. Co-capping of ras proteins with surface immunoglobulins in B lymphocytes. Nature. 1990;347:396
  190. Cheng PC, Dykstra ML, Mitchell RN, Pierce SK. A role for lipid rafts in B cell antigen receptor signaling and antigen targeting. J Exp Med. 1999;190:1549
  191. Hashimoto A, Okada H, Jiang A, et al.  Involvement of guanosine triphosphatases and phospholipase C-gamma2 in extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase activation by the B cell antigen receptor. J Exp Med. 1998;188:1287
  192. Tamir I, Stolpa JC, Helgason CD, et al.  The RasGAP-binding protein p62dok is a mediator of inhibitory FcgammaRIIB signals in B cells. Immunity. 2000;12:347
  193. Gulbins E, Brenner B, Schlottmann K, et al.  Activation of the Ras signaling pathway by the CD40 receptor. J Immunol. 1996;157:2844
  194. Sutherland CL, Heath AW, Pelech SL, Young PR, Gold MR. Differential activation of the ERK, JNK, and p38 mitogen-activated protein kinases by CD40 and the B cell antigen receptor. J Immunol. 1996;157:3381
  195. Healy JI, Dolmetsch RE, Timmerman LA, et al.  Different nuclear signals are activated by the B cell receptor during positive versus negative signaling. Immunity. 1997;6:419
  196. McLeod SJ, Ingham RJ, Bos JL, Kurosaki T, Gold MR. Activation of the Rap1 GTPase by the B cell antigen receptor. J Biol Chem. 1998;273:29218
  197. Lioubin MN, Myles GM, Carlberg K, Bowtell D, Rohrschneider LR. Shc, Grb2, Sos1, and a 150-kilodalton tyrosine-phosphorylated protein form complexes with Fms in hematopoietic cells. Mol Cell Biol. 1994;14:5682
  198. Lee AW, States DJ. Both src-dependent and -independent mechanisms mediate phosphatidylinositol 3-kinase regulation of colony-stimulating factor 1–activated mitogen-activated protein kinases in myeloid progenitors. Mol Cell Biol. 2000;20:6779
  199. Jin DI, Jameson SB, Reddy MA, Schenkman D, Ostrowski MC. Alterations in differentiation and behavior of monocytic phagocytes in transgenic mice that express dominant suppressors of ras signaling. Mol Cell Biol. 1995;15:693
  200. Skorski T, Szczylik C, Ratajczak MZ, et al.  Growth factor-dependent inhibition of normal hematopoiesis by N-ras antisense oligodeoxynucleotides. J Exp Med. 1992;175:743
  201. Mavilio F, Kreider BL, Valtieri M, et al.  Alteration of growth and differentiation factors response by Kirsten and Harvey sarcoma viruses in the IL-3–dependent murine hematopoietic cell line 32D C13(G). Oncogene. 1989;4:301
  202. Maher J, Baker D, Dibb N, Roberts I. Mutant ras promotes haemopoietic cell proliferation or differentiation in a cell-specific manner. Leukemia. 1996;10:83
  203. Hibi S, Lohler J, Friel J, Stocking C, Ostertag W. Induction of monocytic differentiation and tumorigenicity by v-Ha-ras in differentiation arrested hematopoietic cells. Blood. 1993;81:1841
  204. Caron E, Self AJ, Hall A. The GTPase Rap1 controls functional activation of macrophage integrin alphaMbeta2 by LPS and other inflammatory mediators. Curr Biol. 2000;10:974
  205. Self AJ, Caron E, Paterson HF, Hall A. Analysis of R-Ras signalling pathways. J Cell Sci. 2001;114:1357
  206. Geng Y, Gulbins E, Altman A, Lotz M. Monocyte deactivation by interleukin 10 via inhibition of tyrosine kinase activity and the Ras signaling pathway. Proc Natl Acad Sci U S A. 1994;91:8602
  207. Guha M, O'Connell MA, Pawlinski R, et al.  Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression. Blood. 2001;98:1429
  208. Chen GJ, Colombo LL, Lopez MC, Watson RR. Reduction of tumor necrosis factor production by splenocytes from v-Ha- ras oncogene-bearing mice. Cancer Lett. 1993;74:147
  209. Delarue FL, Taylor BS, Sebti SM. Ras and RhoA suppress whereas RhoB enhances cytokine-induced transcription of nitric oxide synthase-2 in human normal liver AKN-1 cells and lung cancer A-549 cells. Oncogene. 2001;20:6531
  210. Ingram DA, Yang FC, Travers JB, et al.  Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo. J Exp Med. 2000;191:181
  211. Hiatt KK, Ingram DA, Zhang Y, Bollag G, Clapp DW. Neurofibromin GTPase-activating protein-related domains restore normal growth in Nf1-/- cells. J Biol Chem. 2001;276:7240
  212. Tsai FY, Orkin SH. Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood. 1997;89:3636
  213. Kitamura Y, Morii E, Jippo T, Ito A. mi-transcription factor as a regulator of mast cell differentiation. Int J Hematol. 2000;71:197
  214. Bar-Sagi D, Gomperts BD. Stimulation of exocytotic degranulation by microinjection of the ras oncogene protein into rat mast cells. Oncogene. 1988;3:463
  215. Prieschl EE, Pendl GG, Harrer NE, Baumruker T. p21ras links Fc epsilon RI to NF-AT family member in mast cells. The AP. 1995;3-like(factor in this cell type is an NF-AT family member. J Immunol 155):4963
  216. Turner H, Cantrell DA. Distinct Ras effector pathways are involved in Fc epsilon R1 regulation of the transcriptional activity of Elk-1 and NFAT in mast cells. J Exp Med. 1997;185:43
  217. Ishizuka T, Terada N, Gerwins P, et al.  Mast cell tumor necrosis factor alpha production is regulated by MEK kinases. Proc Natl Acad Sci U S A. 1997;94:6358
  218. Csonga R, Prieschl EE, Jaksche D, Novotny V, Baumruker T. Common and distinct signaling pathways mediate the induction of TNF-alpha and IL-5 in IgE plus antigen-stimulated mast cells. J Immunol. 1998;160:273
  219. Kimata M, Inagaki N, Kato T, et al.  Roles of mitogen-activated protein kinase pathways for mediator release from human cultured mast cells. Biochem Pharmacol. 2000;60:589
  220. Price LS, Norman JC, Ridley AJ, Koffer A. The small GTPases Rac and Rho as regulators of secretion in mast cells. Curr Biol. 1995;5:68
  221. Matsumura I, Nakajima K, Wakao H, et al.  Involvement of prolonged ras activation in thrombopoietin-induced megakaryocytic differentiation of a human factor-dependent hematopoietic cell line. Mol Cell Biol. 1998;18:4282
  222. Matsumura I, Kawasaki A, Tanaka H, et al.  Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines. Blood. 2000;96:2440
  223. Garcia J, de Gunzburg J, Eychene A, Gisselbrecht S, Porteu F. Thrombopoietin-mediated sustained activation of extracellular signal-regulated kinase in UT7-Mpl cells requires both Ras-Raf-1– and Rap1-B-Raf–dependent pathways. Mol Cell Biol. 2001;21:2659
  224. Ge Y, Li ZH, Marshall MS, Broxmeyer HE, Lu L. Involvement of H-ras in erythroid differentiation of TF1 and human umbilical cord blood CD34 cells. Blood Cells Mol Dis. 1998;24:124
  225. Kang CD, Do IR, Kim KW, et al.  Role of Ras/ERK-dependent pathway in the erythroid differentiation of K562 cells. Exp Mol Med. 1999;31:76
  226. Darley RL, Hoy TG, Baines P, Padua RA, Burnett AK. Mutant N-RAS induces erythroid lineage dysplasia in human CD34+ cells. J Exp Med. 1997;185:1337
  227. Graf T, McNagny K, Brady G, Frampton J. Chicken “erythroid” cells transformed by the Gag-Myb-Ets-encoding E26 leukemia virus are multipotent. Cell. 1992;70:201
  228. Pazdrak K, Schreiber D, Forsythe P, Justement L, Alam R. The intracellular signal transduction mechanism of interleukin 5 in eosinophils (the involvement of lyn tyrosine kinase and the Ras-Raf-1- MEK-microtubule-associated protein kinase pathway). J Exp Med. 1995;181:1827
  229. Hall DJ, Cui J, Bates ME, et al.  Transduction of a dominant-negative H-Ras into human eosinophils attenuates extracellular signal-regulated kinase activation and interleukin-5–mediated cell viability. Blood. 2001;98:2014
  230. Scheele JS, Ripple D, Lubbert M. The role of ras and other low molecular weight guanine nucleotide (GTP)- binding proteins during hematopoietic cell differentiation. Cell Mol Life Sci. 2000;57:1950
  231. MacKenzie KL, Dolnikov A, Millington M, Shounan Y, Symonds G. Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow repopulated mice. Blood. 1999;93:2043
  232. Hawley RG, Fong AZ, Ngan BY, Hawley TS. Hematopoietic transforming potential of activated ras in chimeric mice. Oncogene. 1995;11:1113
  233. Zou X, Calame K. Signaling pathways activated by oncogenic forms of Abl tyrosine kinase. J Biol Chem. 1999;274:18141
  234. Skorski T, Kanakaraj P, Ku DH, et al.  Negative regulation of p120GAP GTPase promoting activity by p210bcr/abl (implication for RAS-dependent Philadelphia chromosome positive cell growth). J Exp Med. 1994;179:1855
  235. Puil L, Liu J, Gish G, et al.  Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. Embo J. 1994;13:764
  236. Pendergast AM, Quilliam LA, Cripe LD, et al.  BCR-ABL–induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell. 1993;75:175
  237. Zou X, Rudchenko S, Wong K, Calame K. Induction of c-myc transcription by the v-Abl tyrosine kinase requires Ras, Raf1, and cyclin-dependent kinases. Genes Dev. 1997;11:654
  238. Skorski T, Bellacosa A, Nieborowska-Skorska M, et al.  Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway. Embo J. 1997;16:6151
  239. Nieborowska-Skorska M, Wasik MA, Slupianek A, et al.  Signal transducer and activator of transcription (STAT)5 activation by BCR/ABL is dependent on intact Src homology (SH)3 and SH2 domains of BCR/ABL and is required for leukemogenesis. J Exp Med. 1999;189:1229
  240. Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell. 1994;77:307
  241. Bollag G, Clapp DW, Shih S, et al.  Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet. 1996;12:144

PII: S0301-472X(02)00904-9

Experimental Hematology
Volume 30, Issue 10 , Pages 1089-1106 , October 2002