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MAPK pathways in radiation responses

Abstract

Within the last 15 years, multiple new signal transduction pathways within cells have been discovered. Many of these pathways belong to what is now termed ‘the mitogen-activated protein kinase (MAPK) superfamily.' These pathways have been linked to the growth factor-mediated regulation of diverse cellular events such as proliferation, senescence, differentiation and apoptosis. Based on currently available data, exposure of cells to ionizing radiation and a variety of other toxic stresses induces simultaneous compensatory activation of multiple MAPK pathways. These signals play critical roles in controlling cell survival and repopulation effects following irradiation, in a cell-type-dependent manner. Some of the signaling pathways activated following radiation exposure are those normally activated by mitogens, such as the ‘classical’ MAPK (also known as the ERK) pathway. Other MAPK pathways activated by radiation include those downstream of death receptors and procaspases, and DNA-damage signals, including the JNK and P38 MAPK pathways. The expression and release of autocrine growth factor ligands, such as (transforming growth factor alpha) and TNF-α, following irradiation can also enhance the responses of MAPK pathways in cells and, consequently, of bystander cells. Thus, the ability of radiation to activate MAPK signaling pathways may depend on the expression of multiple growth factor receptors, autocrine factors and Ras mutation. Enhanced basal signaling by proto-oncogenes such as K-/H-/N-RAS may provide a radioprotective and growth-promoting signal. In many cell types, this may be via the PI3K pathway; in others, this may occur through nuclear factor-kappa B or multiple MAPK pathways. This review will describe the enzymes within the known MAPK signaling pathways and discuss their activation and roles in cellular radiation responses.

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Abbreviations

MAPK:

mitogen-activated protein kinase

MKK:

mitogen-activated protein kinase kinase

MEK:

mitogen-activated/extracellular-regulated kinase

RSK:

ribosomal S6 kinase (S6 K)

NF-κB:

nuclear factor-kappa B

C/EBP:

CCAAT enhancer binding protein

FTI:

farnesyl transferase inhibitor

HSP:

heat-shock protein

PI3K:

phosphatidyl inositol 3-kinase

JNK:

c-Jun NH2-terminal kinase

EGFR:

epidermal growth factor receptor

PTPase:

protein tyrosine phosphatase

TGF:

transforming growth factor

IL:

interleukin; PTEN, phosphatase and tensin homologue on chromosome 10

IGFI-R:

insulin-like growth factor I receptor

References

  • Abbott DW and Holt JT . (1999). J. Biol. Chem., 274, 2732–2742.

  • Ahmed MM, Chendil D, Lele S, Venkatasubbarao K, Dey S, Ritter M, Rowland RG and Mohiuddin M . (2001). Am. J. Clin. Oncol., 24, 500–505.

  • Ahmed MM, Sells SF, Venkatasubbarao K, Fruitwala SM, Muthukkumar S, Harp C, Mohiuddin M and Rangnekar VM . (1997). J. Biol. Chem., 272, 33056–33061.

  • Alessi DR, Caudwell FB, Andjelkovic M, BA Hemmings and Cohen P . (1996). FEBS Lett., 399, 333–338.

  • Amorino GP, Hamilton VM, Valerie K, Dent P, Lammering G and Schmidt-Ullrich RK . (2002). Mol. Biol. Cell., 13, 2233–2244.

  • Aoudjit F and Vuori K . (2001). J. Cell. Biol., 152, 633–643.

  • Assefa Z, Valius M, Vantus T, Agostinis P, Merlevede W and Vandenheede JR . (1999). Biochem. Biophys. Res. Commun., 261, 641–645.

  • Baba I, Shirasawa S, Iwamoto R, Okumura K, Sunoda TT, Nishioka M, Fukuyama K, Yamamoto K, Mekada E and Sasazuki T . (2000). Cancer Res., 60, 6886–6889.

  • Balaban N, Moni J, Shannon M, Dang L, Murphy E and Goldkorn T . (1996). Biochim. Biophys. Acta., 1314, 147–156.

  • Balendran A, Hare GR, Kieloch A, Williams MR and Alessi DR . (2000). FEBS Lett., 484, 217–223.

  • Barradas M, Monjas A, Diaz-Meco MT, Serrano M and Moscat J . (1999). EMBO J., 18, 6362–6369.

  • Bar-Shira A, Rashi-Elkeles S, Zlochover L, Moyal L, Smorodinsky NI, Seger R and Shiloh Y . (2002). Oncogene, 21, 849–855.

  • Bhat-Nakshatri P, Sweeney CJ and Nakshatri H . (2002). Oncogene, 21, 2066–2078.

  • Bosch E, Cherwinski H, Peterson D and McMahon M . (1997). Oncogene, 15, 1021–1033.

  • Boucher MJ, Morisset J, Vachon, PH Reed JC, Laine J and Rivard N . (2000). J. Cell. Biochem., 79, 355–369.

  • Boulton TG and Cobb MH . (1991). Cell Regulat., 2, 357–371.

  • Bowers G, Reardon D, Hewitt T, Dent P, Mikkelsen RB, Valerie K, Lammering G, Amir C and Schmidt-Ullrich RK . (2001). Oncogene, 20, 1388–1397.

  • Broustas CG, Grammatikakis N, Eto M, Dent P, Brautigan DL and Kasid U . (2002). J. Biol.Chem., 277, 3053–3059.

  • Brummer T, Shaw PE, Reth M and Misawa Y . (2002). EMBO J., 21, 5611–5622.

  • Bulavin DV, Amundson SA and Fornace AJ . (2002). Curr. Opin. Genet. Dev., 12, 92–97.

  • Cai H, Smola U, Wixler V, Eisenmann-Tappe I, Diaz-Meco MT, Moscat J, Rapp U and Cooper GM . (1997). Mol. Cell Biol., 17, 732–741.

  • Camandola S and Mattson MP . (2000). J. Neurosci. Res., 61, 134–139.

  • Carter S, Auer KL, Birrer M, Fisher PB, Schmidtt-Ulrich RK, Valerie K, Mikkelsen R and Dent P . (1998). Oncogene, 16, 2787–2796.

  • Chadee DN, Yuasa T and Kyriakis JM . (2002). Mol. Cell. Biol., 22, 737–749.

  • Chen BC and Lin WW . (2001). Br. J. Pharmacol., 134, 1055–1065.

  • Chen J, Fujii K, Zhang L, Roberts T and Fu H . (2001a). Proc. Natl. Acad. Sci. USA, 98, 7783–7788.

  • Chen R, Kim O, Yang J, Sato K, Eisenmann KM, McCarthy J, Chen H and Qiu Y . (2001b). J. Biol. Chem., 276, 31858–31862.

  • Chendil D, Das A, Dey S, Mohiuddin M and Ahmed MM . (2002). Cancer Biol. and Ther., 2, 152–162.

  • Ching TT, Lin HP, Yang CC, Oliveira M, Lu PJ and Chen CS . (2001). J. Biol. Chem., 276, 43932–43938.

  • Coles LC and Shaw PE . (2002). Oncogene, 21, 2236–2244.

  • Contessa JN, Hampton J, Lammering G, Mikkelsen RB, Dent P, Valerie K and Schmidt-Ullrich RK . (2002). Oncogene, 21, 4032–4041.

  • Cremesti A, Paris F, Grassme H, Holler N, Tschopp J, Fuks Z, Gulbins E and Kolesnick R . (2001). J. Biol. Chem., 276, 23954–23961.

  • Cross DA, Alessi DR, Cohen P, Andjelkovich M and Hemmings BA . (1995). Nature, 378, 785–789.

  • Cuello M, Ettenberg SA, Clark AS, Keane MM, Posner RH, Nau MM, Dennis PA and Lipkowitz S . (2001). Cancer Res., 61, 4892–4900.

  • Daly JM, Olayioye MA, Wong AM, Neve R, Lane HA, Maurer FG and Hynes NE . (1999). Oncogene, 18, 3440–3451.

  • Das A, Chendil D, Dey S, Mohiuddin M, Milbrandt J, Rangnekar VM and Ahmed MM . (2001). J. Biol. Chem., 276, 3279–3286.

  • Davis RJ . (1999). Biochem., Soc. Symp., 64, 1–12.

  • Deak MM, Clifton AD, Lucocq LM and Alessi DR . (1998). EMBO J., 17, 4426–4441.

  • De Belle I, Huang RP, Fan Y, Liu C, Mercola D and Adamson ED . (1999). Oncogene, 18, 3633–3642.

  • De Cesare D, Jacquot S, Hanauer A and Sassone-Corsi P . (1998). Proc. Natl. Acad. Sci. USA, 95, 12202–12207.

  • Dent P, Haser W, Haystead TA, Vincent LA, Roberts TM and Sturgill TW . (1992). Science, 257, 1404–1407.

  • Dent P, Jelinek T, Morrison DK, Weber MJ and Sturgill TW . (1995). Science, 268, 1902–1906.

  • Dent P, Reardon DB, Park JS, Bowers G, Logsdon C, Valerie K and Ullrich RK . (1999). Mol. Biol. Cell, 10, 2493–2506.

  • Dent P and Sturgill TW . (1994). Proc. Natl. Acad. Sci. USA, 91, 9544–9548.

  • Derijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M and Davis RJ . (1994). Cell, 76, 1025–1037.

  • Derijard B, Raingeaud J, Barrett T, Wu IH, Han J, Ulevitch RJ and Davis RJ . (1995). Science, 267, 682–685.

  • Dhillon AS, Pollock C, Steen H, Shaw PE, Mischak H and Kolch W . (2002). Mol. Cell. Biol., 22, 3237–3246.

  • Diaz-Meco MT, Lallena MJ, Monjas A, Frutos S and Moscat J . (1999). J. Biol. Chem., 274, 19606–19612.

  • Dickson LM, Lingohr MK, McCuaig J, Hugl SR, Snow L, Kahn BB, Myers MG and Rhodes CJ . (2001). J. Biol. Chem., 276, 21110–21120.

  • Eblen ST, Slack JK, Weber MJ and Catling AD . (2002). Mol. Cell. Biol., 22, 6023–6033.

  • English JM, Pearson G, Hockenberry T, Shivakumar L, White MA and Cobb MH J . (1999). J. Biol. Chem., 274, 31588–31592.

  • English JM, Vanderbilt CA, Xu S, Marcus S and Cobb MH . (1995). J. Biol. Chem., 270, 28897–28902.

  • Erhardt P, Schremser EJ and Cooper GM . (1999). Mol. Cell. Biol., 19, 5308–5315.

  • Fabian JR, Daar IO and Morrison DK . (1993). Mol. Cell Biol., 13, 7170–7179.

  • Filippa N, Sable CL, Hemmings BA and Van Obberghen E . (2000). Cell Biol., 20, 5712–5721.

  • Frost JA, Xu S, Hutchison MR, Marcus S and Cobb MH . (1996). Mol. Cell. Biol., 16, 3707–3713.

  • Fujita E, Jinbo A, Matuzaki H, Konishi H, Kikkawa U and Momoi T . (1999). Biochem. Biophys. Res. Commun., 264, 550–555.

  • Gokhale PC, McRae D, Monia BP, Bagg A, Rahman A, Dritschilo A and Kasid U . (1999). Antisense Nucleic Acid Drug Dev., 9, 191–201.

  • Grana TM, Rusyn EV, Zhou H, Sartor CI and Cox AD . (2002). Cancer Res., 62, 4142–4150.

  • Grant S, Qiao L and Dent P . (2002). Front Biosci., 7, d376–d389.

  • Graves JD, Draves KE, Gotoh Y, Krebs EG and Clark EA . (2001). J. Biol. Chem., 276, 14909–14915.

  • Gu H, Maeda H, Moon JJ, Lord JD, Yoakim M, Nelson BH and Neel BG . (2000). Mol. Cell. Biol., 20, 7109–7120.

  • Guan KL, Figueroa C, Brtva TR, Zhu T, Taylor J, Barber TD and Vojtek AB . (2000). J. Biol. Chem., 275, 27354–23759.

  • Gupta AK, Bakanauskas VJ, Cerniglia GJ, Cheng Y, Bernhard EJ, Muschel RJ and McKenna WG . (2001). Cancer Res., 61, 4278–4782.

  • Gupta AK, Bernhard EJ, Bakanauskas VJ, Wu J, Muschel RJ and McKenna WG . (2000). Radiat. Res., 154, 64–72.

  • Gupta AK, McKenna WG, Weber CN, Feldman MD, Goldsmith JD, Mick R, Machtay M, Rosenthal DI, Bakanauskas VJ, Cerniglia GJ, Bernhard EJ, Weber RS and Muschel RJ . (2002). Clin. Cancer Res., 8, 885–892.

  • Hagan M, Wang L, Hanley JR, Park JS and Dent P . (2000). Radiat. Res., 153, 371–381.

  • Hallahan DE, Dunphy E, Virudachalam S, Sukhatme VP, Kufe DW and Weichselbaum RR . (1995). J. Biol. Chem., 270, 30303–30309.

  • Han J, Lee JD, Bibbs L and Ulevitch RJ . (1994). Science, 265, 808–811.

  • Harada H, Andersen JS, Mann M, Terada N and Korsmeyer SJ . (2001). Proc. Natl. Acad. Sci. USA, 98, 9666–9670.

  • Hayakawa J, Ohmichi M, Kurachi H, Kanda Y, Hisamoto K, Nishio Y, Adachi K, Tasaka K, Kanzaki T and Murata Y . (2000). Cancer Res., 60, 5988–5994.

  • Haystead CM, Wu J, Gregory P, Sturgill TW and Haystead TA . (1993). FEBS Lett., 317, 12–16.

  • Herr I, Wilhelm D, Bohler T, Angel P and Debatin KM . (1997). EMBO J., 16, 6200–6208.

  • Hibi M, Lin A, Smeal T, Minden A and Karin M . (1993). Genes. Dev., 7, 2135–2148.

  • Holbrook NJ, Liu Y and Fornace AJ . (1996). EXS., 77, 273–288.

  • Huang GC, Ouyang X and Epstein RJ . (1998). Biochem. J., 331, 113–119.

  • Huser M, Luckett J, Chiloeches A, Mercer K, Iwobi M, Giblett S, Sun XM, Brown J, Marais R and Pritchard C . (2001). EMBO J., 20, 1940–1951.

  • Jaumot M and Hancock JF . (2001). Oncogene, 20, 3949–3958.

  • Jost M, Huggett TM, Kari C, Boise LH and Rodeck U . (2001). J. Biol. Chem., 276, 6320–6326.

  • Jung M and Dritschilo A . (2001). Semin. Radiat. Oncol., 11, 346–351.

  • Juretic N, Santibanez JF, Hurtado C and Martinez J . (2001). J. Cell. Biochem., 83, 92–98.

  • Kainulainen V, Sundvall M, Maatta JA, Santiestevan E, Klagsbrun M and Elenius K . (2000). J. Biol. Chem., 27, 8641–8649.

  • Kamakura S, Moriguchi T and Nishida E . (1999). J. Biol. Chem., 274, 26563–26571.

  • Kasid U, Suy S, Dent P, Ray S, Whiteside TL and Sturgill TW . (1996). Nature, 382, 813–816.

  • Kato K, Ito H, Iwamoto I, Lida K and Inaguma Y . (2001). Cell Stress Chaperones, 6, 16–20.

  • Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ and Lee JD . (1997). EMBO J., 16, 7054–7066.

  • Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ and Lee JD . (1998). Nature, 395, 713–716.

  • Kavanagh BD, Dent P, Schmidt-Ullrich RK, Chen P and Mikkelsen RB . (1998). Radiation Res., 149, 579–587.

  • Kawabe S, Nishikawa T, Munshi A, Roth JA, Chada S and Meyn RE . (2002). Mol. Ther., 6, 637–644.

  • Kharbanda S, Yuan ZM, Weichselbaum R and Kufe D . (1998). Oncogene, 17, 3309–3318.

  • Kim SJ, Ju JW, Oh CD, Yoon YM, Song WK, Kim JH, Yoo YJ, Bang OS and Kang SS . (2002). J. Biol. Chem., 277, 1332–1339.

  • King AJ, Wireman RS, Hamilton M and Marshall MS . (2001). FEBS Lett., 497, 6–14.

  • Kitagawa D, Tanemura S, Ohata S, Shimizu N, Seo J, Nishitai G, Watanabe T, Nakagawa K, Kishimoto H, Wada T, Tezuka T, Yamamoto T, Nishina H and Katada T . (2002). J. Biol. Chem., 277, 366–371.

  • Klinger M, Kudlacek O, Seidel MG, Freissmuth M and Sexl V . (2002). J. Biol. Chem., 277, 32490–32497.

  • Kuo ML, Chuang SE, Lin MT and Yang SY . (2001). Oncogene, 20, 677–685.

  • Kyriakis JM, App H, Zhang XF, Banerjee P, Brautigan DL, Rapp UR and Avruch J . (1992). Nature, 358, 417–421.

  • Kyriakis JM and Avruch J . (2001). Physiol. Rev., 81, 807–869.

  • Lali FV, Hunt AE, Turner SJ and Foxwell BM . (2000). J. Biol. Chem., 275, 7395–7402.

  • Lammering G, Hewit TH, Hawkins WT, Contessa JN, Reardon DB, Lin PS, Valerie K, Dent P, Mikkelsen RB and Schmidt-Ullrich RK . (2001a). J. Natl. Cancer Inst., 93, 921–929.

  • Lammering G, Lin PS, Contessa JN, Hampton JL, Valerie K and Schmidt-Ullrich RK . (2001b). Int. J. Radiat. Oncol. Biol. Phys., 51, 775–784.

  • Lammering G, Valerie K, Lin PS, Mikkelsen RB, Contessa JN, Feden JP, Farnsworth J, Dent P and Schmidt-Ullrich RK . (2001c). Clin. Cancer Res., 7, 682–690.

  • Lange-Carter CA, Pleiman CM, Gardner AM, Blumer KJ and Johnson GL . (1993). Science, 260, 315–319.

  • Leach JK, Van Tuyle G, Lin PS, Schmidt-Ullrich R and Mikkelsen RB . (2001). Cancer Res., 61, 3894–3901.

  • Lee H, Akita RW, Sliwkowski MX and Maihle NJ . (2001a). Cancer Res., 61, 4467–4473.

  • Lee JT and McCubrey JA . (2002). Leukemia, 16, 486–507.

  • Lee SH, Eom M, Lee SJ, Kim S, Park HJ and Park D . (2001b). J. Biol. Chem., 276, 25066–25072.

  • Lee YJ, Soh JW, Dean NM, Cho CK, Kim TH, Lee SJ and Lee YS . (2002b). Cell Growth Differ., 13, 237–246.

  • Leverrier Y, Thomas J, Mathieu AL, Low W, Blanquier B and Marvel J . (1999). Cell Death Differ., 6, 290–296.

  • Leevers SJ, Paterson HF and Marshall CJ . (1994). Nature, 369, 411–414.

  • Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B and Schlessinger J . (1993). Nature, 363, 85–88.

  • Li Y, Tennekoon GI, Birnbaum M, Marchionni MA and Rutkowski JL . (2001). Mol. Cell. Neurosci., 17, 761–767.

  • Light Y, Paterson H and Marais R . (2002). Mol. Cell. Biol., 22, 4984–4996.

  • Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL and Karin M . (1995). Science, 268, 286–290.

  • Liu B, Fang M, Lu Y, Mills GB and Fan Z . (2001). Br. J. Cancer, 85, 303–311.

  • Lu Y and Settleman J . (1999). Genes Dev., 13, 1168–1180.

  • Mabuchi S, Ohmichi M, Kimura A, Hisamoto K, Hayakawa J, Nishio Y, Adachi K, Takahashi K, Arimoto-Ishida E, Nakatsuji Y, Tasaka K and Murata Y . (2002). J. Biol. Chem., 277, 33490–33500.

  • Maizels ET, Mukherjee A, Sithanandam G, Peters CA, Cottom J, Mayo KE and Hunzicker-Dunn M . (2001). Mol. Endocrinol., 15, 716–733.

  • Marais R, Light Y, Paterson HF and Marshall CJ . (1995). EMBO J., 14, 3136–3145.

  • Marais R, Light Y, Paterson HF, Mason CS and Marshall CJ . (1997). J. Biol. Chem., 272, 4378–4383.

  • McKinstry R, Qiao L, Dai Y, Fisher PB, Grant S and Dent P . (2002). Cancer Biol. and Ther., 1, 241–251.

  • McPherson RA, Harding A, Roy S, Lane A and Hancock JF . (1999). Oncogene, 18, 3862–3869.

  • Meyer RG, Kupper JH, Kandolf R and Rodemann HP . (2002). Eur. J. Biochem., 269, 337–346.

  • Mody N, Leitch J, Armstrong C, Dixon J and Cohen P . (2001). FEBS Lett., 502, 21–24.

  • Moodie SA, Willumsen BM, Weber MJ and Wolfman A . (1993). Science, 260, 1658–1661.

  • Morrison DK, Heidecker G, Rapp UR and Copeland TD . (1993). J. Biol. Chem., 268, 17309–17316.

  • Muller G, Storz P, Bourteele S, Doppler H, Pfizenmaier K, Mischak H, Philipp A, Kaiser C and Kolch W . (1998). EMBO J., 17, 732–742.

  • Munster PN, Marchion DC, Basso AD and Rosen N . (2002). Cancer Res., 62, 3132–3137.

  • Nakamura JL, Arvold ND and Haas-Kogan DA . (2002). Proceedings of the 44th annual ASTRO meeting, 177 (Abstract 1207).

  • Noguchi K, Kitanaka C, Yamana H, Kokubu A, Mochizuki T and Kuchino Y . (1999). J. Biol. Chem., 274, 32580–32587.

  • Olivier JP, Raabe T, Henkemeyer M, Dickson B, Mbamalu G, Margolis B, Schlessinger J, Hafen E and Pawson T . (1993). Cell, 73, 179–191.

  • Panka DJ, Mano T, Suhara T, Walsh K and Mier JW . (2001). J. Biol. Chem., 276, 6893–6896.

  • Pardo OE, Arcaro A, Salerno G, Raguz S, Downward J and Seckl MJ . (2002). J. Biol. Chem., 277, 12040–12046.

  • Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS and Choi EJ . (2002). J. Biol. Chem., 277, 2573–2578.

  • Park JS, Reardon DB, Carter S, Fisher PB, Schmidt-Ullrich RK and Dent P . (1999). Mol. Biol. Cell, 10, 4231–4236.

  • Pianetti S, Arsura M, Romieu-Mourez R, Coffey RJ and Sonenshein GE . (2001). Oncogene, 20, 1287–1299.

  • Podsypanina K, Lee RT, Politis C, Hennessy I, Crane A, Puc J, Neshat M, Wang H, Yang L, Gibbons J, Frost P, Dreisbach V, Blenis J, Gaciong Z, Fisher P, Sawyers C, Hedrick-Ellenson L and Parsons R . (2001). Proc. Natl. Acad. Sci. USA, 98, 10320–10325.

  • Qiao L, Studer E, Leach K, McKinstry R, Gupta S, Decker R, Kukreja R, Valerie K, Nagarkatti P, El Deiry W, Molkentin J, Schmidt-Ullrich RK, Fisher PB, Grant S, Hylemon PB and Dent P . (2001). Mol. Biol. Cell, 12, 2629–2645.

  • Qiao L, Yacoub A, McKinstry R, Park JS, Caron R, Fisher PB, Hagan MP, Grant S and Dent P . (2002). Cancer Biol. Ther., 1, 168–176.

  • Qiu SG, El-Guendy N, Krishnan S and Rangnekar VM . (1999). Oncogene, 18, 7115–7123.

  • Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P and McLeish KR . (2001). J. Biol. Chem., 276, 3517–3523.

  • Reardon DB, Contessa JN, Mikkelsen RB, Valerie K, Amir C, Dent P and Schmidt-Ullrich RK . (1999). Oncogene, 18, 4756–4766.

  • Reusch HP, Zimmermann S, Schaefer M, Paul M and Moelling K . (2001). J. Biol. Chem., 276, 33630–33637.

  • Riccio A, Ahn S, Davenport CM, Blendy JA and Ginty DD . (1999). Science, 286, 2358–2361.

  • Robbins DJ, Zhen E, Owaki H, Vanderbilt CA, Ebert D, Geppert TD and Cobb MH . (1993). J. Biol. Chem., 268, 5097–5106.

  • Rosette C and Karin M . (1996). Science, 274, 1194–1197.

  • Rossomando AJ, Dent P, Sturgill TW and Marshak DR . (1994). Mol. Cell. Biol., 14, 1594–1602.

  • Rubio I, Rodriguez-Viciana P, Downward J and Wetzker R . (1997). Biochem. J., 326, 891–895.

  • Russell JS, Raju U, Gumin GJ, Lang FF, Wilson DR, Huet T and Tofilon PJ . (2002). Cancer Res., 62, 2318–2326.

  • Sarkar D, Su ZZ, Lebedeva IV, Sauane M, Gopalkrishnan RV, Valerie K, Dent P and Fisher PB . (2002a). Proc. Natl. Acad. Sci. USA, 99, 10054–10059.

  • Shao R, Tsai EM, Wei K, von Lindern R, Chen YH, Makino K and Hung MC . (2001). Cancer Res., 61, 7413–7416.

  • Scheid MP, Schubert KM and Duronio V . (1999). J. Biol. Chem., 274, 31108–31113.

  • Schlesinger TK, Fanger GR, Yujiri T and Johnson GL . (1998). Biosciences, 3, D1181–D1186.

  • Schlesinger TK, Bonvin C, Jarpe MB, Fanger GR, Cardinaux JR, Johnson GL and Widmann C . (2002). J. Biol. Chem., 277, 10283–10291.

  • Schmidt-Ullrich RK, Mikkelsen RB, Dent P, Todd DG, Valerie K, Kavanagh BD, Contessa JN, Rorrer WK and Chen PB . (1997). Oncogene, 15, 1191–1197.

  • Schonwasser DC, Marais RM, Marshall CJ and Parker PJ . (1998). Mol. Cell. Biol., 18, 790–798.

  • Shonai T, Adachi M, Sakata K, Takekawa M, Endo T, Imai K and Hareyama M . (2002). Cell Death Differ., 9, 963–971.

  • Sizemore N, Lerner N, Dombrowski N, Sakurai H and Stark GR . (2002). J. Biol. Chem., 277, 3863–3869.

  • Stokoe D and McCormick F . (1997). EMBO J., 16, 2384–2396.

  • Sturgill TW and Ray LB . (1986). Biochem. Biophys. Res. Commun., 134, 565–571.

  • Sturgill TW, Ray LB, Erikson E and Maller JL . (1988). Nature, 334, 715–718.

  • Su ZZ, Lebedeva IV, Sarkar D, Gopalkrishnan RV, Sigmon C, Yacoub A, Valerie K, Dent P and Fisher PB . (2002). Oncogene, 22, 1164–1180.

  • Suhara T, Mano T, Oliveira BE and Walsh K . (2001). Circ. Res., 89, 13–19.

  • Sun H, King AJ, Diaz HB and Marshall MS . (2000). Curr. Biol., 10, 281–284.

  • Sun W, Kesavan K, Schaefer BC, Garrington TP, Ware M, Johnson NL, Gelfand EW and Johnson GL . (2001). J. Biol. Chem., 276, 5093–5100.

  • Suy S, Anderson WB, Dent P, Chang E and Kasid U . (1997). Oncogene, 15, 53–61.

  • Suy S, Wojnowski L, Zimmer A and Kasid U . (2001). 48th Radiat. Res. Soc. Meeting, 155, p. 125 (Abstract P13–164).

  • Suzaki Y, Yoshizumi M, Kagami S, Koyama AH, Taketani Y, Houchi H, Tsuchiya K, Takeda E and Tamaki T . (2002). J. Biol. Chem., 277, 9614–9621.

  • Taher MM, Hershey CM, Oakley JD and Valerie K . (2000). Photochem. Photobiol., 71, 455–459.

  • Tang D, Wu D, Hirao A, Lahti JM, Liu L, Mazza B, Kidd VJ, Mak TW and Ingram AJ . (2002). J. Biol. Chem., 277, 12710–12717.

  • Thorson JA, Yu LWK, Hsu AL, Shih NY, Graves PR, Tanner JW, Allen PM, Piwnica-Worms H and Shaw AS . (1998). Mol. Cell. Biol., 18, 5229–5238.

  • Timokhina I, Kissel H, Stella G and Besmer P . (1998). EMBO J., 17, 6250–6262.

  • Tombes RM, Auer KL, Mikkelsen R, Valerie K, Wymann MP, Marshall CJ, McMahon M and Dent P . (1998). Biochem J., 330, 1451–1460.

  • Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T and Davis RJ . (1999). Mol. Cell. Biol., 19, 1569–1581.

  • Troppmair J, Hartkamp J and Rapp UR . (1998). Oncogene, 17, 685–690.

  • Tuyt LM, Dokter WH, Birkenkamp K, Koopmans SB, Lummen C, Kruijer W and Vellenga E . (1999). J. Immunol., 162, 4893–4902.

  • Tzivion G, Luo J and Avruch J . (1998). Nature, 394, 88–92.

  • Van Elst L, Barr M, Marcus S, Polverino A and Wigler M . (1993). Proc. Natl. Acad. Sci. USA, 90, 6213–6217.

  • Vanhaesebroeck B and Alessi DR . (2000). Biochem. J., 346, 561–576.

  • Van-Weering DH, de Rooij J, Marte B, Downward J, Bos JL and Burgering BM . (1998). Mol. Cell. Biol., 18, 1802–1811.

  • Verheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, Birrer MJ, Szabo E, Zon LI, Kyriakis JM, Haimovitz-Friedman A, Fuks Z and Kolesnick RN . (1996). Nature, 380, 75–79.

  • Virolle T, Adamson ED, Baron V, Birle D, Mercola D, Mustelin T and de Belle I . (2001). Nat. Cell. Biol., 3, 1124–1128.

  • von Gise A, Lorenz P, Wellbrock C, Hemmings B, Berberich-Siebelt F, Rapp UR and Troppmair J . (2001). Mol. Cell. Biol., 21, 2324–2336.

  • Vrana JA, Grant S and Dent P . (1999). Radiat. Res., 151, 559–569.

  • Wang X, McGowan CH, Zhao M, He L, Downey JS, Fearns C, Wang Y, Huang S and Han J . (2000). Mol. Cell. Biol., 20, 4543–4552.

  • Wang YM, Seibenhener ML, Vandenplas ML and Wooten MW . (1999). J. Neurosci. Res., 55, 293–302.

  • Warenius HM, Jones MD and Thompson CC . (1996). Radiat. Res., 146, 485–493.

  • Weldon CB, Scandurro AB, Rolfe KW, Clayton JL, Elliott S, Butler NN, Melnik LI, Alam J, McLachlan JA, Jaffe BM, Beckman BS and Burow ME . (2002). Surgery, 132, 293–301.

  • Widmann C, Gerwins P, Johnson NL, Jarpe MB and Johnson GL . (1998). Mol. Cell. Biol., 18, 2416–2429.

  • Widmann C, Johnson NL, Gardner AM, Smith RJ and Johnson GL . (1997). Oncogene, 15, 2439–2447.

  • Wiggin GR, Soloaga A, Foster JM, Murray-Tait V, Cohen P and Arthur JS . (2002). Mol. Cell. Biol., 22, 2871–2281.

  • Wojnowski L, Stancato LF, Larner AC, Rapp UR and Zimmer A . (2000). Mech. Dev., 91, 97–104.

  • Wojnowski L, Stancato LF, Zimmer AM, Hahn H, Beck TW, Larner AC, Rapp UR and Zimmer A . (1998). Mech. Dev., 76, 141–149.

  • Wojnowski L, Zimmer AM, Beck TW, Hahn H, Bernal R, Rapp UR and Zimmer A . (1997). Nat. Genet., 16, 293–297.

  • Wu J, Harrison JK, Dent P, Lynch KR, Weber MJ and Sturgill TW . (1993). Mol. Cell. Biol., 13, 4539–4548.

  • Wu J, Michel H, Rossomando A, Haystead T, Shabanowitz J, Hunt DF and Sturgill TW . (1992). Biochem. J., 285, 701–705.

  • Wymann MP and Pirola L . (1998). Biochim. Biophys. Acta., 1436, 127–150.

  • Yacoub A, McKinstry R, Hinman D, Chung E, Dent P and Hagan MP . (2003). Radiat. Res., 159, 439–452.

  • Yacoub A, Park JS, Qiao L, Dent P and Hagan MP . (2001). Int. J. Radiat. Biol., 77, 1067–1078.

  • Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR and Templeton DJ . (1994). Nature, 37, 2798–2800.

  • Yang SH, Whitmarsh AJ, Davis RJ and Sharrocks AD . (1998). EMBO J., 17, 1740–1749.

  • Yip-Schneider MT, Miao W, Lin A, Barnard DS, Tzivion G and Marshall MS . (2000). Biochem. J., 351, 151–159.

  • York RD, Molliver DC, Grewal SS, Stenberg PE, McCleskey EW and Stork PJ . (2000). Mol. Cell. Biol., 20, 8069–8083.

  • Yosimichi G, Nakanishi T, Nishida T, Hattori T, Takano-Yamamoto T and Takigawa M . (2001). Eur. J. Biochem., 268, 6058–6065.

  • Yu CF, Roshan B, Liu ZX and Cantley LG . (2001). J. Biol. Chem., 276, 32552–32558.

  • Yustein JT, Li D, Robinson D and Kung HJ . (2000). Oncogene, 19, 710–718.

  • Zhang Y, Dong Z, Nomura M, Zhong S, Chen N and Bode AM . (2001). J. Biol. Chem., 276, 20913–20923.

  • Zhang Y, Ma WY, Kaji A, Bode AM and Dong Z . (2002). J. Biol. Chem., 277, 3124–3131.

  • Zhang Y, Yao B, Delikat S, Bayoumy S, Lin XH, Basu S, McGinley M, Chan-Hui PY, Lichenstein H and Kolesnick R . (1997). Cell, 89, 63–72.

  • Zhou G, Bao ZQ and Dixon JE . (1995). J. Biol. Chem., 270, 12665–12669.

  • Zimmermann S and Moelling K . (1999). Science, 286, 1741–1744.

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Acknowledgements

This research was supported in part by National Institute of Health Grants CA72955, DK52875, CA88906, Department of Defense Grant BC98-0148, the Universal Leaf Corporation and the Chernow Endowment.

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Dent, P., Yacoub, A., Fisher, P. et al. MAPK pathways in radiation responses. Oncogene 22, 5885–5896 (2003). https://doi.org/10.1038/sj.onc.1206701

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