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Alternative p38 MAPK Pathways

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Stress-Activated Protein Kinases

Part of the book series: Topics in Current Genetics ((TCG,volume 20))

Abstract

There are four members of the mammalian p38 mitogen-activated protein kinases (MAPKs) family (p38α, p38β, p38γ and p38δ) which are about 60% identical in their amino acid sequence but differ in their expression patterns, substrate specificities, and sensitivities to chemical inhibitors such as SB203580. Much attention in recent years has been focused on studying the role of the p38α isoform, which is widely referred to as p38 in the literature. However, there are other p38 isoforms (p38β, p38γ and p38δ) whose roles among the cellular functions and the implication in some of the pathological conditions have not been precisely defined so far. Here, we focus on the emergent roles of the alternative p38γ and p38δ MAPK pathways and their implication in different biological processes. It is now clear that these p38MAPKs show similarities to the classical p38MAPK, but with some differences that challenge the paradigm of the archetypical p38MAPK pathway.

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References

  1. Abdollahi T, Robertson NM, Abdollahi A, Litwack G (2003) Identification of interleukin 8 as an inhibitor of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in the ovarian carcinoma cell line OVCAR3. Cancer Res 63:4521–4526

    PubMed  CAS  Google Scholar 

  2. Alonso G, Ambrosino C, Jones M, Nebreda AR (2000) Differential activation of p38 mitogen-activated protein kinase isoforms depending on signal strength. J Biol Chem 275:40641–40648

    Article  PubMed  CAS  Google Scholar 

  3. Ambrose M, Ryan A, O'Sullivan GC, Dunne C, Barry OP (2006) Induction of apoptosis in renal cell carcinoma by reactive oxygen species: involvement of extracellular signal-regulated kinase 1/2, p38delta/gamma, cyclooxygenase-2 down-regulation, and translocation of apoptosis-inducing factor. Mol Pharmacol 69:1879–1890

    Article  PubMed  CAS  Google Scholar 

  4. Balasubramanian S, Efimova T, Eckert RL (2002) Green tea polyphenol stimulates a Ras, MEKK1, MEK3, and p38 cascade to increase activator protein 1 factor-dependent involucrin gene expression in normal human keratinocytes. J Biol Chem 277:1828–1836

    Article  PubMed  CAS  Google Scholar 

  5. Beardmore VA, Hinton HJ, Eftychi C, Apostolaki M, Armaka M, Darragh J, McIlrath J, Carr JM, Armit LJ, Clacher C, Malone L, Kollias G, Arthur JS (2005) Generation and characterization of p38beta (MAPK11) gene-targeted mice. Mol Cell Biol 25:10454–10464

    Article  PubMed  CAS  Google Scholar 

  6. Brancho D, Tanaka N, Jaeschke A, Ventura JJ, Kelkar N, Tanaka Y, Kyuuma M, Takeshita T, Flavell RA, Davis RJ (2003) Mechanism of p38 MAP kinase activation in vivo. Genes Dev 17:1969–1978

    Article  PubMed  CAS  Google Scholar 

  7. Chiariello M, Marinissen MJ, Gutkind JS (2000) Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-Jun promoter and to cellular transformation. Mol Cell Biol 20:1747–1758

    Article  PubMed  CAS  Google Scholar 

  8. Cohen P (1997) The search for physiological substrate of MAP and SAP kinases in mammalian cells. Trends Cell Biol 7:353–361

    Article  PubMed  CAS  Google Scholar 

  9. Conrad PW, Rust RT, Han J, Millhorn DE, Beitner-Johnson D (1999) Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells. J Biol Chem 274:23570–23576

    Article  PubMed  CAS  Google Scholar 

  10. Court NW, dos Remedios CG, Cordell J, Bogoyevitch MA (2002) Cardiac expression and subcellular localization of the p38 mitogen-activated protein kinase member, stress-activated protein kinase-3 (SAPK3). J Mol Cell Cardiol 34:413–426

    Article  PubMed  CAS  Google Scholar 

  11. Court NW, Kuo I, Quigley O, Bogoyevitch MA (2004) Phosphorylation of the mitochondrial protein Sab by stress-activated protein kinase 3. Biochem Biophys Res Commun 319:130–137

    Article  PubMed  CAS  Google Scholar 

  12. Crnogorac-Jurcevic T, Efthimiou E, Capelli P, Blaveri E, Baron A, Terris B, Jones M, Tyson K, Bassi C, Scarpa A, Lemoine NR (2001) Gene expression profiles of pancreatic cancer and stromal desmoplasia. Oncogene 20:7437–7446

    Article  PubMed  CAS  Google Scholar 

  13. Cuenda A, Cohen P (1999) Stress-activated protein kinase-2/p38 and a rapamycin-sensitive pathway are required for C2C12 myogenesis. J Biol Chem 274:4341–4346

    Article  PubMed  CAS  Google Scholar 

  14. Cuenda A, Cohen P, Buee-Scherrer V, Goedert M (1997) Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular stresses is mediated via SAPKK3 (MKK6); comparison of the specificities of SAPK3 and SAPK2 (RK/p38). EMBO J 16:295–305

    Article  PubMed  CAS  Google Scholar 

  15. Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR, Lee JC (1995) SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett 364:229–233

    Article  PubMed  CAS  Google Scholar 

  16. Dashti SR, Efimova T, Eckert RL (2001) MEK6 regulates human involucrin gene expression via a p38alpha- and p38delta-dependent mechanism. J Biol Chem 276:27214–27220

    Article  PubMed  CAS  Google Scholar 

  17. Davies SP, Reddy H, Caivano M, Cohen P (2000) Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J 351:95–105

    Article  PubMed  CAS  Google Scholar 

  18. Diehl NL, Enslen H, Fortner KA, Merritt C, Stetson N, Charland C, Flavell RA, Davis RJ, Rincon M (2000) Activation of the p38 mitogen-activated protein kinase pathway arrests cell cycle progression and differentiation of immature thymocytes in vivo. J Exp Med 191:321–34

    Article  PubMed  CAS  Google Scholar 

  19. Eckert RL, Crish JF, Efimova T, Dashti SR, Deucher A, Bone F, Adhikary G, Huang G, Gopalakrishnan R, Balasubramanian S (2004) Regulation of involucrin gene expression. J Invest Dermatol 123:13–22

    Article  PubMed  CAS  Google Scholar 

  20. Eckert RL, Efimova T, Balasubramanian S, Crish JF, Bone F, Dashti S (2003) p38 Mitogen-activated protein kinases on the body surface–a function for p38 delta. J Invest Dermatol 120:823–828

    Article  PubMed  CAS  Google Scholar 

  21. Efimova T, Broome AM, Eckert RL (2003) A regulatory role for p38 delta MAPK in keratinocyte differentiation. Evidence for p38 delta-ERK1/2 complex formation. J Biol Chem 278:34277–34285

    Article  PubMed  CAS  Google Scholar 

  22. Efimova T, Broome AM, Eckert RL (2004) Protein kinase Cdelta regulates keratinocyte death and survival by regulating activity and subcellular localization of a p38delta-extracellular signal-regulated kinase 1/2 complex. Mol Cell Biol 24:8167–8183

    Article  PubMed  CAS  Google Scholar 

  23. Enslen H, Brancho DM, Davis RJ (2000) Molecular determinants that mediate selective activation of p38 MAP kinase isoforms. EMBO J 19:1301–1311

    Article  PubMed  CAS  Google Scholar 

  24. Enslen H, Raingeaud J, Davis RJ (1998) Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. J Biol Chem 273:1741–1748

    Article  PubMed  CAS  Google Scholar 

  25. Eyers PA, Craxton M, Morrice N, Cohen P, Goedert M (1998) Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive forms by a single amino-acid substitution. Chem Biol 5:321–328

    Article  PubMed  CAS  Google Scholar 

  26. Faccio L, Chen A, Fusco C, Martinotti S, Bonventre JV, Zervos AS (2000) Mxi2, a splice variant of p38 stress-activated kinase, is a distal nephron protein regulated with kidney ischemia. Am J Physiol Cell Physiol 278:C781–C790

    PubMed  CAS  Google Scholar 

  27. Feijoo C, Campbell DG, Jakes R, Goedert M, Cuenda A (2005) Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly. J Cell Sci 118:397–408

    Article  PubMed  CAS  Google Scholar 

  28. Goedert M, Cuenda A, Craxton M, Jakes R, Cohen P (1997a) Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases. EMBO J 16:3563–3571

    Article  PubMed  CAS  Google Scholar 

  29. Goedert M, Hasegawa M, Jakes R, Lawler S, Cuenda A, Cohen P (1997b) Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases. FEBS Lett 409:57–62

    Article  PubMed  CAS  Google Scholar 

  30. Gross EA, Callow MG, Waldbaum L, Thomas S, Ruggieri R (2002) MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest. J Biol Chem 277:13873–82

    Article  PubMed  CAS  Google Scholar 

  31. Gum RJ, McLaughlin MM, Kumar S, Wang Z, Bower MJ, Lee JC, Adams JL, Livi GP, Goldsmith EJ, Young PR (1998) Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket. J Biol Chem 273:15605–15610

    Article  PubMed  CAS  Google Scholar 

  32. Han J, Lee JD, Bibbs L, Ulevitch RJA (1994) MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265:808–811

    Article  PubMed  CAS  Google Scholar 

  33. Hasegawa M, Cuenda A, Spillantini MG, Thomas GM, Buee-Scherrer V, Cohen P, Goedert M (1999) Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition. J Biol Chem 274:12626–12631

    Article  PubMed  CAS  Google Scholar 

  34. Jans R, Atanasova G, Jadot M, Poumay Y (2004) Cholesterol depletion upregulates involucrin expression in epidermal keratinocytes through activation of p38. J Invest Dermatol 123:564–573

    Article  PubMed  CAS  Google Scholar 

  35. Jenkins SM, Zinnerman M, Garner C, Johnson GV (2000) Modulation of Tau phosphorylation and intracellular localization by cellular stress. Biochem J 345:263–270

    Article  PubMed  CAS  Google Scholar 

  36. Jiang Y, Chen C, Li Z, Guo W, Gegner JA, Lin S, Han J (1996) Characterization of the structure and function of a new mitogen-activated protein kinase (p38beta). J Biol Chem 271:17920–17926

    Article  PubMed  CAS  Google Scholar 

  37. Jiang Y, Gram H, Zhao M, New L, Gu J, Feng L, Di Padova F, Ulevitch RJ, Han J (1997) Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. J Biol Chem 272:30122–30128

    Article  PubMed  CAS  Google Scholar 

  38. Johansen C, Kragballe K, Westergaard M, Henningsen J, Kristiansen K, Iversen L (2005) The mitogen-activated protein kinases p38 and ERK1/2 are increased in lesional psoriatic skin. Br J Dermatol 152:37–42

    Article  PubMed  CAS  Google Scholar 

  39. Keum YS, Yu S, Chang PP, Yuan X, Kim JH, Xu C, Han J, Agarwal A, Kong AN (2006) Mechanism of action of sulforaphane: inhibition of p38 mitogen-activated protein kinase isoforms contributing to the induction of antioxidant response element-mediated heme oxygenase-1 in human hepatoma HepG2 cells. Cancer Res 66:8804–8813

    Article  PubMed  CAS  Google Scholar 

  40. Kim JM, White JM, Shaw AS, Sleckman BP (2005) MAPK p38 alpha is dispensable for lymphocyte development and proliferation. J Immunol 174:1239–1244

    PubMed  CAS  Google Scholar 

  41. Knebel A, Haydon CE, Morrice N, Cohen P (2002) Stress-induced regulation of eukaryotic elongation factor 2 kinase by SB 203580-sensitive and -insensitive pathways. Biochem J 367:525–532

    Article  PubMed  CAS  Google Scholar 

  42. Knebel A, Morrice N, Cohen P (2001) A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. EMBO J 20:4360–4369

    Article  PubMed  CAS  Google Scholar 

  43. Kraft CA, Efimova T, Eckert RL (2007) Activation of PKCdelta and p38delta MAPK during okadaic acid dependent keratinocyte apoptosis. Arch Dermatol Res 2007 Jan 26: [Epub ahead of print]

    Google Scholar 

  44. Kuma Y, Campbell DG, Cuenda A (2004) Identification of glycogen synthase as a new substrate for stress-activated protein kinase 2b/p38beta. Biochem J 379:133–139

    Article  PubMed  CAS  Google Scholar 

  45. Kuma Y, Sabio G, Bain J, Shpiro N, Marquez R, Cuenda A (2005) BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J Biol Chem 280:19472–19479

    Article  PubMed  CAS  Google Scholar 

  46. Lechner C, Zahalka MA, Giot JF, Moller NP, Ullrich A (1996) ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation. Proc Natl Acad Sci USA 93:4355–4359

    Article  PubMed  CAS  Google Scholar 

  47. Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, Strickler JE, McLaughlin MM, Siemens IR, Fisher SM, Livi GP, White JR, Adams JL, Young PR (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372:739–746

    Article  PubMed  CAS  Google Scholar 

  48. Liu ZG, Baskaran R, Lea-Chou ET, Wood LD, Chen Y, Karin M, Wang JY (1996) Three distinct signalling responses by murine fibroblasts to genotoxic stress. Nature 384:273–276

    Article  PubMed  CAS  Google Scholar 

  49. Liu LX, Liu ZH, Jiang HC, Zhang WH, Qi SY, Hu J, Wang XQ, Wu M (2003) Gene expression profiles of hepatoma cell line HLE. World J Gastroenterol 9:683–687

    PubMed  CAS  Google Scholar 

  50. Lluis F, Perdiguero E, Nebreda AR, Munoz-Canoves P (2006) Regulation of skeletal muscle gene expression by p38 MAP kinases. Trends Cell Biol 16:36–44

    Article  PubMed  CAS  Google Scholar 

  51. Marinissen MJ, Chiariello M, Gutkind JS (2001) Regulation of gene expression by the small GTPase Rho through the ERK6 (p38 gamma) MAP kinase pathway. Genes Dev 15:535–553

    Article  PubMed  CAS  Google Scholar 

  52. Mertens S, Craxton M, Goedert M (1996) SAP kinase-3, a new member of the family of mammalian stress-activated protein kinases. FEBS Lett 383:273–276

    Article  PubMed  CAS  Google Scholar 

  53. Morrison DK, Davis RJ (2003) Regulation of MAP kinase signaling modules by scaffold proteins in mammals. Annu Rev Cell Dev Biol 19:91–118

    Article  PubMed  CAS  Google Scholar 

  54. Nishigaki K, Thompson D, Yugawa T, Rulli K, Hanson C, Cmarik J, Gutkind JS, Teramoto H, Ruscetti S (2003) Identification and characterization of a novel Ste20/germinal center kinase-related kinase, polyploidy-associated protein kinase. J Biol Chem 278:13520–13530

    Article  PubMed  CAS  Google Scholar 

  55. Pargellis C, Tong L, Churchill L, Cirillo PF, Gilmore T, Graham AG, Grob PM, Hickey ER, Moss N, Pav S, Regan J (2002) Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nat Struct Biol 9:268–272

    Article  PubMed  CAS  Google Scholar 

  56. Parker CG, Hunt J, Diener K, McGinley M, Soriano B, Keesler GA, Bray J, Yao Z, Wang XS, Kohno T, Lichenstein HS (1998) Identification of stathmin as a novel substrate for p38 delta. Biochem Biophys Res Commun 249:791–796

    Article  PubMed  CAS  Google Scholar 

  57. Perdiguero E, Pillaire MJ, Bodart JF, Hennersdorf F, Frodin M, Duesbery NS, Alonso G, Nebreda AR (2003) Xp38gamma/SAPK3 promotes meiotic G(2)/M transition in Xenopus oocytes and activates Cdc25C. EMBO J 22:5746–5756

    Article  PubMed  CAS  Google Scholar 

  58. Pramanik R, Qi X, Borowicz S, Choubey D, Schultz RM, Han J, Chen G (2003) p38 isoforms have opposite effects on AP-1-dependent transcription through regulation of c-Jun. The determinant roles of the isoforms in the p38 MAPK signal specificity. J Biol Chem 278:4831–4839

    Article  PubMed  CAS  Google Scholar 

  59. Qi X, Tang J, Loesch M, Pohl N, Alkan S, Chen G (2006) p38gamma mitogen-activated protein kinase integrates signaling crosstalk between Ras and estrogen receptor to increase breast cancer invasion. Cancer Res 66:7540–7547

    Article  PubMed  CAS  Google Scholar 

  60. Sabio G, Arthur JS, Kuma Y, Peggie M, Carr J, Murray-Tait V, Centeno F, Goedert M, Morrice NA, Cuenda A (2005) p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP. EMBO J 24:1134–1145

    Article  PubMed  CAS  Google Scholar 

  61. Sabio G, Reuver S, Feijoo C, Hasegawa M, Thomas GM, Centeno F, Kuhlendahl S, Leal-Ortiz S, Goedert M, Garner C, Cuenda A (2004) Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2. Biochem J 380:19–30

    Article  PubMed  CAS  Google Scholar 

  62. Sakabe K, Teramoto H, Zohar M, Behbahani B, Miyazaki H, Chikumi H, Gutkind JS (2002) Potent transforming activity of the small GTP-binding protein Rit in NIH 3T3 cells: evidence for a role of a p38gamma-dependent signaling pathway. FEBS Lett 511:15–20

    Article  PubMed  CAS  Google Scholar 

  63. Sanz-Moreno V, Casar B, Crespo P (2003) p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its nuclear activity by sustaining its phosphorylation levels. Mol Cell Biol 23:3079–3090

    Article  PubMed  CAS  Google Scholar 

  64. Singh US, Pan J, Kao YL, Joshi S, Young KL, Baker KM (2003) Tissue transglutaminase mediates activation of RhoA and MAP kinase pathways during retinoic acid-induced neuronal differentiation of SH-SY5Y cells. J Biol Chem 278:391–399

    Article  PubMed  CAS  Google Scholar 

  65. Stein B, Yang MX, Young DB, Janknecht R, Hunter T, Murray BW, Barbosa MS (1997) p38-2, a novel mitogen-activated protein kinase with distinct properties. J Biol Chem 272:19509–19517

    Article  PubMed  CAS  Google Scholar 

  66. Sudo T, Yagasaki Y, Hama H, Watanabe N, Osada H (2002) Exip, a new alternative splicing variant of p38 alpha, can induce an earlier onset of apoptosis in HeLa cells. Biochem Biophys Res Commun 291:838–843

    Article  PubMed  CAS  Google Scholar 

  67. Tanaka N, Kamanaka M, Enslen H, Dong C, Wysk M, Davis RJ, Flavell RA (2002) Differential involvement of p38 mitogen-activated protein kinase kinases MKK3 and MKK6 in T-cell apoptosis. EMBO Rep 3:785–791

    Article  PubMed  CAS  Google Scholar 

  68. Tang J, Qi X, Mercola D, Han J, Chen G (2005) Essential role of p38gamma in K-Ras transformation independent of phosphorylation. J Biol Chem 280:23910–23917

    Article  PubMed  CAS  Google Scholar 

  69. Tortorella LL, Lin CB, Pilch PF (2003) ERK6 is expressed in a developmentally regulated manner in rodent skeletal muscle. Biochem Biophys Res Commun 306:163–168

    Article  PubMed  CAS  Google Scholar 

  70. Wang L, Ma R, Flavell RA, Choi ME (2002) Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for activation of p38alpha and p38delta MAPK isoforms by TGF-beta 1 in murine mesangial cells. J Biol Chem 277:47257–47262

    Article  PubMed  CAS  Google Scholar 

  71. Wang X, McGowan CH, Zhao M, He L, Downey JS, Fearns C, Wang Y, Huang S, Han J (2000) Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol 20:4543–4552

    Article  PubMed  CAS  Google Scholar 

  72. Yagasaki Y, Sudo T, Osada H (2004) Exip, a splicing variant of p38alpha, participates in interleukin-1 receptor proximal complex and downregulates NF-kappaB pathway. FEBS Lett 575:136–140

    Article  PubMed  CAS  Google Scholar 

  73. Yin J, Liu YH, Xu YF, Zhang YJ, Chen JG, Shu BH, Wang JZ (2006) Melatonin arrests peroxynitrite-induced tau hyperphosphorylation and the overactivation of protein kinases in rat brain. J Pineal Res 41:124–129

    Article  PubMed  CAS  Google Scholar 

  74. Yoshida H, Goedert M (2006) Sequential phosphorylation of tau protein by cAMP-dependent protein kinase and SAPK4/p38delta or JNK2 in the presence of heparin generates the AT100 epitope. J Neurochem 99:154–164

    Article  PubMed  CAS  Google Scholar 

  75. Zervos AS, Faccio L, Gatto JP, Kyriakis JM, Brent R (1995) Mxi2, a mitogen-activated protein kinase that recognizes and phosphorylates Max protein. Proc Natl Acad Sci USA 92:10531–10534

    Article  PubMed  CAS  Google Scholar 

  76. Zhang QS, Maddock DA, Chen JP, Heo S, Chiu C, Lai D, Souza K, Mehta S, Wan YS (2001) Cytokine-induced p38 activation feedback regulates the prolonged activation of AKT cell survival pathway initiated by reactive oxygen species in response to UV irradiation in human keratinocytes. Int J Oncol 19:1057–1061

    PubMed  CAS  Google Scholar 

  77. Zhu X, Rottkamp CA, Hartzler A, Sun Z, Takeda A, Boux H, Shimohama S, Perry G, Smith MA (2001) Activation of MKK6, an upstream activator of p38, in Alzheimer's disease. J Neurochem 79:311–318

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ana Cuenda .

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Francesc Posas Angel R. Nebreda

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Iñesta-Vaquera, F., Sabio, G., Kuma, Y., Cuenda, A. (2007). Alternative p38 MAPK Pathways. In: Posas, F., Nebreda, A.R. (eds) Stress-Activated Protein Kinases. Topics in Current Genetics, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/4735_2007_0239

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