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Oncogenes and Tumor Suppressor Genes in Human Malignancies pp 265–279Cite as

Signal transduction by receptor tyrosine kinases

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Part of the book series: Cancer Treatment and Research ((CTAR,volume 63))

Abstract

Many oncogenes exert proliferative effects on cells by influencing signal transduction pathways. Signal transduction provides a means for cells to propagate and amplify signals received from the environment to specific targets within the cell. The culmination of this pathway is DNA synthesis and cell division. Since growth is not a common event in organs of mature multicellular organisms, these pathways must be precisely regulated. The signalling process begins at the cytoplasmic membrane, where cell surface receptors interact with growth factors that are either soluble or present on other cells or in the extracellular matrix. Nontransformed cultured cells require exogenously supplied growth factors to stimulate proliferation and growth [1]. In contrast, transformed cells exhibit partial to complete relaxation of the requirements for growth factors, and factor dependence can be abrogated by the expression of oncogenes or activated forms of proto-oncogenes [1]. Oncogene products are able to overide factor dependency by mimicking the actions of ligands, their receptors, or downstream signals in the ordered procession of events that follow mitogenic stimulation [2]. Each control point in the signal transduction pathway is a potential target of deregulation by oncoproteins. Thus, an understanding of how tumorigenic events affect the cell’s dependence upon growth factors requires the identification of these control points and the characterization of the interactions between the components of the signal transduction machinery.

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References

  1. Cross M, Dexter TM: Growth factors in development, transformation, and tumorigenesis. Cell 64:271–280, 1991.

    Article  PubMed  CAS  Google Scholar 

  2. Bishop JM: Molecular themes in oncogenesis. Cell 64, 235–248, 1991.

    Article  PubMed  CAS  Google Scholar 

  3. Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antonidades HN: Simian sarcoma virus one gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275–277, 1983.

    Article  PubMed  CAS  Google Scholar 

  4. Waterfield MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wasteson A, Westermark B, Heldin C-H, Huang JS, Deuel TF: Platelet-derived growth factor is structurally related to the putative transforming protein p28s“ of simian sarcoma virus. Nature 304:35–39, 1983.

    Article  PubMed  CAS  Google Scholar 

  5. Ross R, Raines EW, Bowen-Pope DF: The biology of platelet-derived growth factor. Cell 46:155–169, 1986.

    Article  PubMed  CAS  Google Scholar 

  6. Hannink M, Donoghue DJ: Structure and function of platelet-derived growth factor (PDGF) and related proteins. Biochim Biophys Acta 989:1–10, 1989.

    PubMed  CAS  Google Scholar 

  7. Ullrich A, Schlessinger J: Signal transduction by receptors with tyrosine kinase activity. Cell 61:203–212, 1990.

    Article  PubMed  CAS  Google Scholar 

  8. Cantley LC, Auger K, Carpenter C, Duckworth B, Graziani A, Kapeller R, Solotof S: Oncogenes and signal transduction. Cell 64:281–304, 1991.

    Article  PubMed  CAS  Google Scholar 

  9. Williams LT: Signal transduction by the platelet-derived growth factor receptor. Science 243:1564–1570, 1989.

    Article  PubMed  CAS  Google Scholar 

  10. Kaplan DR, Whitman M, Schaffhausen B, Pallas DC, White M, Cantley L, Roberts TM: Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity. Cell 50:1021–1029, 1987.

    Article  PubMed  CAS  Google Scholar 

  11. Coughlin SR, Escobedo JA, Williams LT: Role of phosphatidylinositol kinase in PDGF receptor signal transduction. Science 243:1191–1194, 1989.

    Article  PubMed  CAS  Google Scholar 

  12. Molloy CJ, Bottaro DP, Fleming TP, Marshall MS, Gibbs JB, Aaronson SA: PDGF induction of tyrosine phosphorylation of GTPase activating protein. Nature 342:711–714, 1989.

    Article  PubMed  CAS  Google Scholar 

  13. Kazalauskas A, Cooper JA: Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins. Cell 58:1121–1133, 1989.

    Article  Google Scholar 

  14. Kumjian DA, Wahl MI, Rhee SG, Daniel TO: Platelet-derived growth factor (PDGF) binding promotes physical association of PDGF receptor with phospholipase C. Proc Natl Acad Sci USA 86:8232–8236, 1989.

    Article  PubMed  CAS  Google Scholar 

  15. Morrison DK, Kaplan DR, Escobedo JA, Rapp UR, Roberts TM, Williams LT: Direct activation of the serine-threonine kinase activity of Raf-1 through tyrosine phosphorylation by the PDGF ß-receptor. Cell 58:649–657, 1989.

    Article  PubMed  CAS  Google Scholar 

  16. Morrison DK, Kaplan DR, Rhee SG, Williams LT: Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-y with the PDGF receptor signaling complex. Mol Cell Biol 10:2359–2366, 1990.

    PubMed  CAS  Google Scholar 

  17. Kazlauskas A, Ellis C, Pawson T, Cooper JA: Binding of GAP to activated PDGF receptors. Science 247:1578–1581, 1990.

    Article  PubMed  CAS  Google Scholar 

  18. Kypta RM, Goldberg Y, Ulug ET, Courtneidge SA: Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell 62:481–492, 1990.

    Article  PubMed  CAS  Google Scholar 

  19. Kaplan DR, Morrison DK, Wong G, McCormick F, Williams LT: PDGF ß-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complex. Cell 61:125–133, 1990.

    Article  PubMed  CAS  Google Scholar 

  20. Cohen B, Yoakim M, Piwnica-Worms H, Roberts TM, Schaffhausen BS: Tyrosine phosphorylation is a signal for the trafficking of pp85, an 85-kDa phosphorylated polypeptide associated with phosphatidylinositol kinase activity. Proc Natl Acad Sci USA 87:4458–4462, 1990.

    Article  PubMed  CAS  Google Scholar 

  21. Todderud G, Wahl MI, Rhee SG, Carpenter G: Stimulation of phospholipase C-gl membrane association by epidermal growth factor. Science 249:296–298, 1990.

    Article  PubMed  CAS  Google Scholar 

  22. Moran MF, Polakis P, McCormick F, Pawson T, Ellis C: Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of P21“ GTPase-activating protein. Mol Cell Biol 11:1840–1812, 1991.

    Google Scholar 

  23. Meisenhelder J, Suh P-G, Rhee SG, Hunter T: Phospholipase C-y is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro. Cell 57:1109–1122, 1989.

    Article  PubMed  CAS  Google Scholar 

  24. Courtneidge SA, Kypta RM, Cooper JA, Kazlauskas A: Platelet-derived growth factor receptor sequences important for binding of src family tyrosine kinases. Cell Growth Diff 2:483–486, 1991.

    PubMed  CAS  Google Scholar 

  25. Escobedo JA, Kaplan DR, Kavanaugh WM, Truck CW, Williams LT: A phosphatidylinositol-3 kinase binds to platelet-derived growth factor receptor sequence containing phosphotyrosine. Mol Cell Biol 11:1124–1132, 1991.

    Google Scholar 

  26. Pawson T: NOn-catalytic domains of cytoplasmic protein-tyrosine kinases: Regulatory elements in signal transduction. Oncogene 3:491–495, 1988.

    PubMed  CAS  Google Scholar 

  27. Anderson D, Koch CA, Grey L, Ellis C, Moran M, Pawson T: Binding of SH2 domains of phospholipase C-g, GAP and Src to activated growth factor receptors. Science 250: 979–982, 1990.

    Article  PubMed  CAS  Google Scholar 

  28. Moran MF, Koch CA, Anderson D, Ellis C, England L, Martin GS, Pawson T: Src ho’mology region 2 domains direct protein-protein interactions in signal transduction. Proc Natl Acad Sci USA 87:8622–8626, 1990.

    Article  PubMed  CAS  Google Scholar 

  29. Margolis B, Bellot F, Honegger AM, Ullrich A, Schlessinger J, Zilbertstein A: Tyrosine kinase activity is essential for the association of phospholipase C-y with the epidermal growth factor receptor. Mol Cell Biol 10:435–441, 1990.

    PubMed  CAS  Google Scholar 

  30. Margolis B, Li N, Koch A, Mohammadi M, Hurwitz DR, Zilbertstein A, Ullrich A, Pawson T, Schlessinger J: The tyrosine phosphorylated carboxyterminus of the EGF receptor is a binding site for GAP and PLC-y. EMBO J 9:4375-4380, 1990.

    Google Scholar 

  31. Escobedo JA, Navankasattusas S, Kavanaugh WM, Mifay D, Fried VA, Williams LT: Purification and cDNA cloning of novel 85 kD protein that has SH2 domains, binds to the tyrosine phosphorylated PDGF-b receptor and regulates binding of PI3-kinase to the receptor. Cell 65:75–82, 1991.

    Article  PubMed  CAS  Google Scholar 

  32. Skolnik JWM, Margolis B, Mohammadi M, Lowenstein E, Fisher R, Drepps A, Ullrich A, Schlessinger J: Cloning of P13-kinase associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell 65:83–90, 1991.

    Article  PubMed  CAS  Google Scholar 

  33. Mohammadi M, Honegger AM, Rotin D, Fischer R, Bellot F, Li W, Dionne CA, Jaye M, Rubinstein, Schlessinger J: A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Fig) is a binding site for the SH2 domain of phospholipase C-yl. Mol Cell Biol 11:5068–6078, 1991.

    PubMed  CAS  Google Scholar 

  34. Wahl MI, Olashaw NE, Nishibe S, Rhee SG, Pledger WJ, Carpenter G: Platelet-derived growth factor induces rapid and sustained tyrosine phosphorylation of phospholipase C-y in quiescent BALB/c 3T3 cells. Mol Cell Biol 9:2934–2943, 1989.

    PubMed  CAS  Google Scholar 

  35. Morrison DK, Kaplan DR, Rapp U, Roberts TM: Signal transduction from membrane to cytoplasm: Growth factors and membrane-bound oncogene products increase Raf-1 phosphorylation and associated protein kinase activity. Proc Natl Acad Sci USA 85:8855–8859, 1988.

    Article  PubMed  CAS  Google Scholar 

  36. Nishibe S, Wahl MI, Hernandez-Sotomayor SMT, Tonks NK, Rhee SG, Carpenter G: Increase of the catalytic activity of phospholipase C-yl by tyrosine phosphorylation. Science 250:1253–1256, 1990.

    Article  PubMed  CAS  Google Scholar 

  37. Kim HK, Kim JW, Zilbertstein A, Margolis B, Kim JG, Schlessinger J, Rhee SG: PDGF stimulation of inositol phospholipid hydrolysis requires PLC-y phosphorylation on tyrosine residues 783 and 1254. Cell 65:435–441, 1991.

    Article  PubMed  CAS  Google Scholar 

  38. Mayer BJ, Hamaguchi M, Hanafusa H: A novel viral oncogene with structural similarity to phospholipase C. Nature 332:272–275, 1988.

    Article  PubMed  CAS  Google Scholar 

  39. Bellacosa A, Testa JR, Staal SP, Tsichlis PN: A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region. Science 254:274–277, 1991.

    Article  PubMed  CAS  Google Scholar 

  40. Plutzky J, Neel BG, Rosenberg RD: Isolation of a sre homology 2-containing tyrosine phosphatase. Proc Natl Acad Sci USA 89:1123–1127, 1992.

    Article  PubMed  CAS  Google Scholar 

  41. Sugimoto Y, Whitman M, Cantley LC, Erikson RL: Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol. Proc Natl Acad Sci USA 81:2117–2121, 1984.

    Article  PubMed  CAS  Google Scholar 

  42. Macara IG, Marinetti GV, Balduzzi PC: Transforming protein of avian sarcoma virus UR2 is associated with phosphatidylinositol kinase activity: Possible role in tumorigenesis. Proc Natl Acad Sci USA 81:2728–2732, 1984.

    Article  PubMed  CAS  Google Scholar 

  43. Whitman M, Kaplan DR, Schaffhausen B, Cantley L, Roberts TM: Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature 315:239–242, 1985.

    Article  PubMed  CAS  Google Scholar 

  44. Kaplan DR, Whitman M, Schaffhausen B, Raptis L, Garcea RL, Pallas D, Roberts TM, Cantley L: Phosphatidylinositol metabolism and polyoma-mediated transformation. Proc Natl Acad Sci USA 83:3624–3628, 1986.

    Article  PubMed  CAS  Google Scholar 

  45. Courtneidge SA, Heber A: An 81 kd protein complexed with middle T antigen and pp60Circ: A possible phosphatidylinositol kinase. Cell 50:1031–1037, 1987.

    Article  PubMed  CAS  Google Scholar 

  46. Fukui Y, Kornbluth S, Jong SM, Wang LH, Hanafusa H: Phosphatidylinositol kinase type I activity associates with various oncogene products. Oncogene Res 4:283–292, 1989.

    PubMed  CAS  Google Scholar 

  47. Reedijk M, Liu X, Pawson T: Interactions of phosphatidylinositol kinase, GTPase-activating protein (GAP), and GAP-associated proteins with the colony-stimulating factor 1 receptor. Mol Cell Biol 10:5601–5608, 1990.

    PubMed  CAS  Google Scholar 

  48. Shurtleff SA, Downing JR, Rock CO, Hawkins SA, Roussel MF, Sherr CJ: Structural features of the colony-stimulating factor 1 receptor that affect its association with phosphatidylinositol 3-kinase. EMBO J 9:2415–2421, 1990.

    PubMed  CAS  Google Scholar 

  49. Bjorge JD, Chan T-O, Antczak M, Kung H-J, Fujita DJ: Activated type 1 phosphatidylinositol kinase is associated with the epidermal growth factor (EGF) receptor following EGF stimulation. Proc Natl Acad Sci USA 87:3816–3820, 1990.

    Article  PubMed  CAS  Google Scholar 

  50. Endemann G, Yonezawa K, Roth RA: Phosphatidylinositol kinase or an associated protein is a substrate for the insulin receptor tyrosine kinase. J Biol Chem 265:396–400, 1990.

    PubMed  CAS  Google Scholar 

  51. Ruderman NB, Kapeller R, White MF, Cantley LC: Activation of phosphatidylinositol 3-kinase by insulin. Proc Natl Acad Sci USA 87:1411–1415, 1990.

    Article  PubMed  CAS  Google Scholar 

  52. Varticovski L, Druker B, Morrison D, Cantley L, Roberts T: The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase. Nature 342: 699–702, 1989.

    Article  PubMed  CAS  Google Scholar 

  53. Varticovski L, Daley G, Jackson P, Baltimore D, Cantley L: Activation of PI3-kinase in cells expressing abl oncogene variants. Mol Cell Biol 11, in press.

    Google Scholar 

  54. Herbst R, Lammers R, Schlessinger J, Ullrich A: Substrate phosphorylation specificity of the human c-kit receptor tyrosine kinase. J Biol Chem 266:19908–19916, 1991.

    PubMed  CAS  Google Scholar 

  55. Rottapel R, Reedijk M, Williams DE, Lyman SD, Anderson DM, Pawson T, Bernstein A: The SteellW transduction pathway: Kit autophosphorylation and its association with a unique subset of cytoplasmic signaling proteins is induced by the Steel factor. Mol Cell Biol 11:3043–3051, 1991.

    PubMed  CAS  Google Scholar 

  56. Lev S, Givol D, Yarden Y: Interkinase domain of kit contains the binding site for phosphatidylinositol 3’ kinase. Proc Natl Acad Sci USA 89:678–682, 1992.

    Article  PubMed  CAS  Google Scholar 

  57. Choudhury GG, Wang L-M, Pierce J, Harvey SA, Sakaguchi AY: A mutational analysis of phosphatidylinositol-3-kinase activation by human colony-stimulating factor-1 receptor. J Biol Chem 266:8068–8072, 1991.

    PubMed  CAS  Google Scholar 

  58. Sun XJ, Rothenberg P, Kahn CR, Backer JM, Araki E, Wilden PA, Cahill DA, Goldstein BJ, White MF: Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352:73–76, 1991.

    Article  PubMed  CAS  Google Scholar 

  59. Auger KR, Carpenter CL, Cantley LC, Varticovski L: Phosphatidylinositol 3-kinase and its novel product, phosphatidylinositol 3-phosphate, are present in Saccharomyces cerevisiae. J Biol Chem 264:20181–20184, 1989.

    PubMed  CAS  Google Scholar 

  60. Whitman M, Downes CP, Keeler M, Keller T, Cantley L: Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phospatidylinositol-3 phosphate. Nature 332:644–646, 1988.

    Article  PubMed  CAS  Google Scholar 

  61. Auger KR, Serunian LA, Soltoff SP, Libby P, Cantley LC: PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell 57:167–175, 1989.

    Article  PubMed  CAS  Google Scholar 

  62. Whitman M, Kaplan D, Roberts T, Cantley L: Evidence for two distinct phosphatidylinositol kinases in fibroblasts: Implications for cellular regulation. Biochem J 247:165–174, 1987.

    PubMed  CAS  Google Scholar 

  63. Morgan WC, Kaplan DR, Pallas DC, Roberts TM: Recombinant retroviruses that transduce middle T antigen cDNAs derived from polyomavirus mutants: Separation of focus formation and soft-agar growth in transformation assays and correlations with kinase activities in vitro. J Virol 62:3407–3414, 1988.

    PubMed  CAS  Google Scholar 

  64. Talmage DA, Freund R, Young AT, Dahl J, Dawe CJ, Benjamin TL: Phosphorylation of middle T by pp60csrc: A switch for binding of phosphatidylinositol 3-kinase and optimal tumorigenesis. Cell 59:55–65, 1989.

    Article  PubMed  CAS  Google Scholar 

  65. Fukui Y, Hanafusa H: Phosphatidylinositol kinase activity associates with viral p60src protein. Mol Cell Biol 9:1651–1658, 1989.

    PubMed  CAS  Google Scholar 

  66. Chan TO, Tanaka A, Bjorge JD, Fujita DJ: Association of type 1 phosphatidylinositol kinase activity with mutationally activated forms of human pp60cjrc. Mol Cell Biol 10:3280–3283, 1990.

    PubMed  CAS  Google Scholar 

  67. Serunian LA, Auger KR, Roberts T, Cantley LC: Production of novel polyphosphoinositides in vivo is linked to transformation by polyoma virus middle T antigen. J Virol 64:4718–4725, 1989.

    Google Scholar 

  68. Carpenter CL, Duckworth BC, Auger KR, Cohen B, Schaffhausen BS, Cantley, LC: Purification and characterization of phosphoinositide 3-kinase from rat liver. J Biol Chem 265:19704–19711, 1990.

    PubMed  CAS  Google Scholar 

  69. Otsu M, Hiles I, Gout I, Fry MJ, Ruiz-Larrea F, Panayotou G, Thompson A, Dhand R, Hsuan J, Totty N, Smith AD, Moryan, SJ, Courtneidge SA, Parker PJ, Waterfield MD: Characterization of two 85 Kd proteins that associate with receptor tyrosine kinases, middle T-pp60cs“ complexes, and phosphatidylinositol-3 kinase. Cell 65:91–104, 1991.

    Article  PubMed  CAS  Google Scholar 

  70. Margolis B, Rhee SG, Felder S, Mervic M, Lyall R, Levitzki A, Ullrich A, Zilbertstein A, Schlessinger J: EGF induces tyrosine phosphorylation of phospholipase C-II: A potential mechanism for EGF receptor signaling. Cell 57:1101–1107, 1989.

    Article  PubMed  CAS  Google Scholar 

  71. Vetter ML, Martin-Zanca D, Parada LF, Bishop JM, Kaplan DR: NGF rapidly stimulates tyrosine phosphorylation of phospholipase C-y by a kinase activity associated with the product of the trk proto-oncogene. Proc Natl Acad Sci USA 88:5650–5654, 1991.

    Article  PubMed  CAS  Google Scholar 

  72. Burgess WH, Dionne CA, Kaplow, J, Mudd R, Friesel R, Zilbertstein A, Schlessinger J, Jaye M: Characterization and cDNA cloning of phospholipase C-y, a major substrate for heparin binding growth factor 1 (acidic fibroblast growth factor) activated tyrosine kinase. Mol Cell Biol 10:4770–4777, 1990.

    PubMed  CAS  Google Scholar 

  73. Whitman M, Cantley L: Phosphoinositide metabolism and the control of cell proliferation. Biochim. Biophys Acta 948:327–344, 1988.

    CAS  Google Scholar 

  74. Rhee SF, Suh P-G, Ryu S-H, Lee SY: Studies of inositol phospholipid-specific phospholipase C. Science 244:546–550, 1989.

    Article  PubMed  CAS  Google Scholar 

  75. Gilman MZ: The c-fos serum response element responds to protein kinase C-dependent and-independent signals but to cyclic AMP. Genes Dev 2:394–402, 1988.

    Article  PubMed  CAS  Google Scholar 

  76. Downward J, Graves JD, Warne PH, Rayter S, Cantrell DA: Stimulation of p21“ upon T-cell activation. Nature 346:719–723, 1990.

    Article  PubMed  CAS  Google Scholar 

  77. Matuoka K, Fukami K, Nakanishi O, Kawai S, Takenawa T: Mitogenesis in response to PDGF and bombesin abolished by microinjection of antibody to PIP2. Science 239: 640–643, 1988.

    Article  PubMed  CAS  Google Scholar 

  78. Smith MR, Heidecker G, Rapp UR, Kung H-F: Induction of transformation and DNA synthesis after microinjection of raf proteins. Mol Cell Biol 10:3828–3833, 1990.

    PubMed  CAS  Google Scholar 

  79. Hill TD, Dean NM, Mordan LJ, Lau AF, Kanemitsu MY, Boynton AL: PDGF-induced activation of phospholipase C is not required for induction of DNA synthesis. Science 248:1660–1663, 1990.

    Article  PubMed  CAS  Google Scholar 

  80. Ellis C, Moran M, McCormick F, Pawson T: Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases. Nature 343:377–381, 1990.

    Article  PubMed  CAS  Google Scholar 

  81. McCormick F: ras GTPase activating protein: Signal transmitter and signal terminator. Cell 56:5–8, 1989.

    Article  PubMed  CAS  Google Scholar 

  82. Tsai M-H, Roudebush M, Dobrowolski S, Yu C-L, Gibbs JR, Stacey DW: Ras GTPase-activating protein physically associates with mitogenically active phospholipids. Mol Cell Biol 11:2785–2793, 1991.

    PubMed  CAS  Google Scholar 

  83. App H, Hazan R, Zilbertstein A, Ullrich A, Schlessinger J, Rapp U: Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1 with the EGF receptor. Mol Cell Biol 11:913–919, 1991.

    PubMed  CAS  Google Scholar 

  84. Morrison DK: The Raf-1 kinase as a transducer of mitogenic signals. Cancer Cells 2: 377–382, 1990.

    PubMed  CAS  Google Scholar 

  85. Li P, Wood K, Mamon H, Haser W, Roberts T: Raf-1: A kinase currently without a cause but not lacking in effects. Cell 64:479–482, 1991.

    Article  PubMed  CAS  Google Scholar 

  86. Heidecker G, Kolch W, Morrison DK, Rapp UR: The role of Raf-1 phosphorylation in signal transduction. In: Vander Woude G (ed): Academic Press, 1991.

    Google Scholar 

  87. Baccarini M, Sabatini DM, App H, Rapp UR, Stanley ER: Colony stimulating factor-1 (CSF-1) stimulates temperature dependent phosphorylation and activation and activation of the Raf-1 proto-oncogene product. EMBO J 9:3649–3657, 1990.

    PubMed  CAS  Google Scholar 

  88. Blackshear PJ, Haupt DM, App H, Rapp UR: Insulin activates the Raf-1 protein kinase. J Biol Chem 265:12131–12134, 1990.

    PubMed  CAS  Google Scholar 

  89. Choudhury GG, Sylvia VL, Pfeifer A, Wang LM, Smith EA, Sakaguchi AY: Human colony stimulating factor-1 receptor activates the c-Raf-1 proto-oncogene kinase. Biochim Biophys Acta 172:154–159, 1990.

    CAS  Google Scholar 

  90. Kovacina KS, Yonezawa K, Brautigan DL, Tonks NK, Rapp UR, Roth RA: Insulin activates the kinase activity of the Raf-1 proto-oncogene by increasing its serine phosphorylation. J Biol Chem 265:12115–12118, 1990.

    PubMed  CAS  Google Scholar 

  91. Kolch W, Heidecker G, Lloyd P, Rapp UR: Raf-1 protein kinase is required for growth of induced NIH/3T3 cells. Nature 349:426–428, 1991.

    Article  PubMed  CAS  Google Scholar 

  92. Ralston R, Bishop JM: The product of the proto-oncogene c-src is modified during the cellular response to platelet-derived growth factor. Proc Natl Acad Sci USA 82:7845–7849, 1985.

    Article  PubMed  CAS  Google Scholar 

  93. Gould K, Hunter T: Platelet-derived growth factor induces multisite phosphorylation of pp60c-src and increases its protein-tyrosine kinase activity. Mol Cell Biol 8:3345–3356, 1988.

    PubMed  CAS  Google Scholar 

  94. Wasilenko WJ, Payne DM, Fitzgerald DL, Weber MJ: Phosphorylation and activation of epidermal growth factor receptors in cells transformed by the sre oncogene. Mol Cell Biol 11:309–321, 1991.

    PubMed  CAS  Google Scholar 

  95. Williams NG, Roberts TM, Li P: Both p21ras and pp6Osrc’’ are required, but neither alone is sufficient to activate the Raf-1 kinase. Proc Natl Acad Sci USA 89:2922–2926, 1992.

    Article  PubMed  CAS  Google Scholar 

  96. Yaish P, Gazit A, Gilon C, Levitzki A: Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors. Science 242:933–935, 1988.

    Article  PubMed  CAS  Google Scholar 

  97. Gazit A, Yaish P, Gilon C, Levitzki A: Tyrophostins I. Synthesis and biological activity of protein tyrosine kinase inhibitors. J Med Chem 32:2344–2352, 1989.

    Article  PubMed  CAS  Google Scholar 

  98. Berg MM, Sternberg DW, Parada LF, Chao MV: K-252a inhibits nerve growth factor-induced trk proto-oncogene tyrosine phosphorylation and kinase activity. J Biol Chem 267:13–16, 1992.

    PubMed  CAS  Google Scholar 

  99. Knusel B, Kaplan DR, Winslow JW, Rosenthal A, Burton LE, Beck KD, Rabin S, Nikolics K, Hefti F: K-252b selectively potentiates cellular actions and trk tyrosine phosphorylation mediated by neutotrophin-3. J Neurochem 59:715–722, 1992.

    Article  PubMed  CAS  Google Scholar 

  100. Hempstead BL, Rabin SJ, Kaplan L, Reid S, Parada L, Kaplan DR: Overexpression of the trk tyrosine kinase rapidly accelerates nerve growth factor-induced differentiation. Neuron, in press.

    Google Scholar 

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Authors
  1. David R. Kaplan
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  2. Archibald Perkins
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  3. Deborah K. Morrison
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Editors and Affiliations

  1. Cancer Research Institute, University of California, San Francisco, USA

    Christopher C. Benz

  2. Lineberger Cancer Research Center, The University of North Carolina at Chapel Hill, USA

    Edison T. Liu

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Kaplan, D.R., Perkins, A., Morrison, D.K. (1993). Signal transduction by receptor tyrosine kinases. In: Benz, C.C., Liu, E.T. (eds) Oncogenes and Tumor Suppressor Genes in Human Malignancies. Cancer Treatment and Research, vol 63. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3088-6_13

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