Skip to main content
SpringerLink
Log in

Regulation of gene expression in response to osmostress by the yeast stress-activated protein kinase Hog1

  • Chapter
  • First Online:
Stress-Activated Protein Kinases

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

Abstract

Exposure of cells to an increase in extracellular osmolarity results in rapid activation of a highly conserved stress-activated protein kinase (SAPK) pathway, known in the budding yeast Saccharomyces cerevisiae as the HOG pathway. Activation of the HOG pathway is essential for the induction of adaptive responses required for cell survival upon osmostress. Regulation of gene expression is a major adaptive response required for cell survival in response to osmostress. The HOG pathway controls gene expression through several mechanisms, such as direct regulation of transcription factor activities, the recruitment of the RNA Polymerase II at osmoresponsive promoters and chromatin modification via recruitment of the Rpd3 histone deacetylase complex. Moreover, recent studies have shown that SAPKs can be recruited to the coding regions of osmostress genes acting as a transcriptional elongation factor. This review summarizes the current knowledge on the regulation of gene expression by the SAPK Hog1 and discusses new insights from yeast that could be relevant to mammals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alepuz PM, de Nadal E, Zapater M, Ammerer G, Posas F (2003) Osmostress-induced transcription by Hot1 depends on a Hog1-mediated recruitment of the RNA Pol II. EMBO J 22:2433–2442

    Article  PubMed  CAS  Google Scholar 

  2. Alepuz PM, Jovanovic A, Reiser V, Ammerer G (2001) Stress-induced MAP kinase Hog1 is part of transcription activation complexes. Mol Cell 7:767–777

    Article  PubMed  CAS  Google Scholar 

  3. Berkes CA, Tapscott SJ (2005) MyoD and the transcriptional control of myogenesis. Semin Cell Dev Biol 16:585–595

    Article  PubMed  CAS  Google Scholar 

  4. Bernstein BE, Tong JK, Schreiber SL (2000) Genomewide studies of histone deacetylase function in yeast. Proc Natl Acad Sci USA 97:13708–13713

    Article  PubMed  CAS  Google Scholar 

  5. Carrozza MJ, Li B, Florens L, Suganuma T, Swanson SK, Lee KK, Shia WJ, Anderson S, Yates J, Washburn MP, Workman JL (2005) Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123:581–592

    Article  PubMed  CAS  Google Scholar 

  6. Causton HC, Ren B, Koh SS, Harbison CT, Kanin E, Jennings EG, Lee TI, True HL, Lander ES, Young RA (2001) Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12:323–337

    PubMed  CAS  Google Scholar 

  7. Chellappan SP (2001) HOG on the promoter: regulation of the osmotic stress response. Sci STKE 31:PE1

    Google Scholar 

  8. Clayton AL, Mahadevan LC (2003) MAP kinase-mediated phosphoacetylation of histone H3 and inducible gene regulation. FEBS Lett 546:51–58

    Article  PubMed  CAS  Google Scholar 

  9. Cullen PJ, Sabbagh W Jr, Graham E, Erick MM, van Olden EK, Neal C, Delray J, Bardwell L, Sprague GF Jr (2004) A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast. Genes Dev 18:1695–1708

    Article  PubMed  CAS  Google Scholar 

  10. Dan I, Watanabe NM, Kurume A (2001) The Ste20 group kinases as regulators of MAP kinase cascades. Trends Cell Biol 11:220–230

    Article  PubMed  CAS  Google Scholar 

  11. Dard N, Peter M (2006) Scaffold proteins in MAP kinase signaling: more than simple passive activating platforms. Bioassays 28:146–156

    Article  CAS  Google Scholar 

  12. de Angelis L, Zhao J, Androecia JJ, Olson EN, Cosset G, McDermott JC (2005) Regulation of vertebrate myotome development by the p38 MAP kinase-MEF2 signaling pathway. Dev Biol 283:171–179

    Article  PubMed  CAS  Google Scholar 

  13. de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3:735–740

    Article  PubMed  CAS  Google Scholar 

  14. de Nadal E, Casadome L, Posas F (2003) Targeting the MEF2-like transcription factor Smp1 by the stress-activated Hog1 mitogen-activated protein kinase. Mol Cell Biol 23:229–237

    Article  PubMed  CAS  Google Scholar 

  15. de Nadal E, Zapater M, Alepuz PM, Sumoy L, Mas G, Posas F (2004) The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 427:370–374

    Article  PubMed  CAS  Google Scholar 

  16. De W, Reiter W, Ballerina A, Ammerer G, Brocade C (2005) A dual role for PP1 in shaping the Msn2-dependent transcriptional response to glucose starvation. EMBO J 24:4115–4123

    Article  CAS  Google Scholar 

  17. Deckert J, Struhl K (2001) Histone acetylation at promoters is differentially affected by specific activators and repressors. Mol Cell Biol 21:2726–2735

    Article  PubMed  CAS  Google Scholar 

  18. Durchschlag E, Reiter W, Ammerer G, Schuller C (2004) Nuclear localization destabilizes the stress-regulated transcription factor Msn2. J Biol Chem 279:55425–55432

    Article  PubMed  CAS  Google Scholar 

  19. Dyson MH, Thomson S, Inagaki M, Goto H, Arthur SJ, Nightingale K, Iborra FJ, Mahadevan LC (2005) MAP kinase-mediated phosphorylation of distinct pools of histone H3 at S10 or S28 via mitogen- and stress-activated kinase 1/2. J Cell Sci 118:2247–2259

    Article  PubMed  CAS  Google Scholar 

  20. Edmunds JW, Mahadevan LC (2004) MAP kinases as structural adaptors and enzymatic activators in transcription complexes. J Cell Sci 117:3715–3723

    Article  PubMed  CAS  Google Scholar 

  21. Edmunds JW, Mahadevan LC (2006) Cell signaling. Protein kinases seek close encounters with active genes. Science 313:449–451

    Article  PubMed  CAS  Google Scholar 

  22. Ferreira ME, Hermann S, Prochasson P, Workman JL, Berndt KD, Wright AP (2005) Mechanism of transcription factor recruitment by acidic activators. J Biol Chem 280:21779–21784

    Article  PubMed  CAS  Google Scholar 

  23. Ferrigno P, Posas F, Koepp D, Saito H, Silver PA (1998) Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1. EMBO J 17:5606–5614

    Article  PubMed  CAS  Google Scholar 

  24. Garcia-Gimeno MA, Struhl K (2000) Aca1 and Aca2, ATF/CREB activators in Saccharomyces cerevisiae, are important for carbon source utilization but not the response to stress. Mol Cell Biol 20:4340–4349

    Article  PubMed  CAS  Google Scholar 

  25. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257

    PubMed  CAS  Google Scholar 

  26. Gorner W, Durchschlag E, Martinez-Pastor MT, Estruch F, Ammerer G, Hamilton B, Ruis H, Schuller C (1998) Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Genes Dev 12:586–597

    Article  PubMed  CAS  Google Scholar 

  27. Gorner W, Durchschlag E, Wolf J, Brown EL, Ammerer G, Ruis H, Schuller C (2002) Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor. EMBO J 21:135–144

    Article  PubMed  CAS  Google Scholar 

  28. Hohmann S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66:300–372

    Article  PubMed  CAS  Google Scholar 

  29. Jacoby T, Flanagan H, Faykin A, Seto AG, Mattison C, Ota I (1997) Two protein-tyrosine phosphatases inactivate the osmotic stress response pathway in yeast by targeting the mitogen-activated protein kinase, Hog1. J Biol Chem 272:17749–17755

    Article  PubMed  CAS  Google Scholar 

  30. Keogh MC, Kurdistani SK, Morris SA, Ahn SH, Podolny V, Collins SR, Schuldiner M, Chin K, Punna T, Thompson NJ, Boone C, Emili A, Weissman JS, Hughes TR, Strahl BD, Grunstein M, Greenblatt JF, Buratowski S, Krogan NJ (2005) Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 123:593–605

    Article  PubMed  CAS  Google Scholar 

  31. Klipp E, Nordlander B, Kruger R, Gennemark P, Hohmann S (2005) Integrative model of the response of yeast to osmotic shock. Nat Biotechnol 23:975–982

    Article  PubMed  CAS  Google Scholar 

  32. Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869

    PubMed  CAS  Google Scholar 

  33. Maeda T, Takekawa M, Saito H (1995) Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science 269:554–558

    Article  PubMed  CAS  Google Scholar 

  34. Maeda T, Wurgler-Murphy SM, Saito H (1994) A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 369:242–245

    Article  PubMed  CAS  Google Scholar 

  35. Marquez JA, Pascual-Ahuir A, Proft M, Serrano R (1998) The Ssn6-Tup1 repressor complex of Saccharomyces cerevisiae is involved in the osmotic induction of HOG-dependent and -independent genes. EMBO J 17:2543–2553

    Article  PubMed  CAS  Google Scholar 

  36. Martinez-Pastor MT, Marchler G, Schuller C, Marchler-Bauer A, Ruis H, and Estruch F (1996) The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J 15:2227–2235

    PubMed  CAS  Google Scholar 

  37. Mason PB, Struhl K (2005) Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo. Mol Cell 17:831–840

    Article  PubMed  CAS  Google Scholar 

  38. Mattison CP, Ota IM (2000) Two protein tyrosine phosphatases, Ptp2 and Ptp3, modulate the subcellular localization of the Hog1 MAP kinase in yeast. Genes Dev 14:1229–1235

    PubMed  CAS  Google Scholar 

  39. McKinsey TA, Zhang CL, Olson EN (2002) MEF2: a calcium-dependent regulator of cell division, differentiation and death. Trends Biochem Sci 27:40–47

    Article  PubMed  CAS  Google Scholar 

  40. Millar CB, Grunstein M (2006) Genome-wide patterns of histone modifications in yeast. Nat Rev Mol Cell Biol 7:657–666

    Article  PubMed  CAS  Google Scholar 

  41. Nehlin JO, Carlberg M, Ronne H (1992) Yeast SKO1 gene encodes a bZIP protein that binds to the CRE motif and acts as a repressor of transcription. Nucleic Acids Res 20:5271–5278

    Article  PubMed  CAS  Google Scholar 

  42. O'Rourke SM, Herskowitz I (2002) A third osmosensing branch in Saccharomyces cerevisiae requires the Msb2 protein and functions in parallel with the Sho1 branch. Mol Cell Biol 22:4739–4749

    Article  PubMed  CAS  Google Scholar 

  43. Pascual-Ahuir A, Posas F, Serrano R, Proft M (2001) Multiple levels of control regulate the yeast cAMP-response element-binding protein repressor Sko1p in response to stress. J Biol Chem 276:37373–37378

    Article  PubMed  CAS  Google Scholar 

  44. Pascual-Ahuir A, Struhl K, Proft M (2006) Genome-wide location analysis of the stress-activated MAP kinase Hog1 in yeast. Methods 40:272–278

    Article  PubMed  CAS  Google Scholar 

  45. Pokholok DK, Zeitlinger J, Hannett NM, Reynolds DB, Young RA (2006) Activated signal transduction kinases frequently occupy target genes. Science 313:533–536

    Article  PubMed  CAS  Google Scholar 

  46. Posas F, Chambers JR, Heyman JA, Hoeffler JP, de Nadal E, Arino J (2000) The transcriptional response of yeast to saline stress. J Biol Chem 275:17249–17255

    Article  PubMed  CAS  Google Scholar 

  47. Posas F, Saito H (1997) Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. Science 276:1702–1705

    Article  PubMed  CAS  Google Scholar 

  48. Posas F, Saito H (1998) Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator. EMBO J 17:1385–1394

    Article  PubMed  CAS  Google Scholar 

  49. Posas F, Witten EA, Saito H (1998) Requirement of STE50 for osmostress-induced activation of the STE11 mitogen-activated protein kinase kinase kinase in the high-osmolarity glycerol response pathway. Mol Cell Biol 18:5788–5796

    PubMed  CAS  Google Scholar 

  50. Posas F, Wurgler-Murphy SM, Maeda T, Witten EA, Thai TC, Saito H (1996) Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 "two-component" osmosensor. Cell 86:865–875

    Article  PubMed  CAS  Google Scholar 

  51. Proft M, Gibbons FD, Copeland M, Roth FP, Struhl K (2005) Genomewide identification of Sko1 target promoters reveals a regulatory network that operates in response to osmotic stress in Saccharomyces cerevisiae. Eukaryot Cell 4:1343–1352

    Article  PubMed  CAS  Google Scholar 

  52. Proft M, Mas G, de Nadal E, Vendrell A, Noriega N, Struhl K, Posas F (2006) The stress-activated Hog1 kinase is a selective transcriptional elongation factor for genes responding to osmotic stress. Mol Cell 23:241–250

    Article  PubMed  CAS  Google Scholar 

  53. Proft M, Pascual-Ahuir A, de Nadal E, Arino J, Serrano R, Posas F (2001) Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in response to osmotic stress. EMBO J 20:1123–1133

    Article  PubMed  CAS  Google Scholar 

  54. Proft M, Serrano R (1999) Repressors and upstream repressing sequences of the stress-regulated ENA1 gene in Saccharomyces cerevisiae: bZIP protein Sko1p confers HOG-dependent osmotic regulation. Mol Cell Biol 19:537–546

    PubMed  CAS  Google Scholar 

  55. Proft M, Struhl K (2002) Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress. Mol Cell 9:1307–1317

    Article  PubMed  CAS  Google Scholar 

  56. Proft M, Struhl K (2004) MAP kinase-mediated stress relief that precedes and regulates the timing of transcriptional induction. Cell 118:351–361

    Article  PubMed  CAS  Google Scholar 

  57. Raitt DC, Posas F, Saito H (2000) Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation of the Hog1 MAPK pathway. EMBO J 19:4623–4631

    Article  PubMed  CAS  Google Scholar 

  58. Reiser V, Ruis H, Ammerer G (1999) Kinase activity-dependent nuclear export opposes stress-induced nuclear accumulation and retention of Hog1 mitogen-activated protein kinase in the budding yeast Saccharomyces cerevisiae. Mol Biol Cell 10:1147–1161

    PubMed  CAS  Google Scholar 

  59. Reiser V, Salah SM, Ammerer G (2000) Polarized localization of yeast Pbs2 depends on osmostress, the membrane protein Sho1 and Cdc42. Nat Cell Biol 2:620–627

    Article  PubMed  CAS  Google Scholar 

  60. Rep M, Krantz M, Thevelein JM, Hohmann S (2000) The transcriptional response of Saccharomyces cerevisiae to osmotic shock. Hot1p and Msn2p/Msn4p are required for the induction of subsets of high osmolarity glycerol pathway-dependent genes. J Biol Chem 275:8290–8300

    Article  PubMed  CAS  Google Scholar 

  61. Rep M, Proft M, Remize F, Tamas M, Serrano R, Thevelein JM, Hohmann S (2001) The Saccharomyces cerevisiae Sko1p transcription factor mediates HOG pathway-dependent osmotic regulation of a set of genes encoding enzymes implicated in protection from oxidative damage. Mol Microbiol 40:1067–1083

    Article  PubMed  CAS  Google Scholar 

  62. Rep M, Reiser V, Gartner U, Thevelein JM, Hohmann S, Ammerer G, Ruis H (1999) Osmotic stress-induced gene expression in Saccharomyces cerevisiae requires Msn1p and the novel nuclear factor Hot1p. Mol Cell Biol 19:5474–5485

    PubMed  CAS  Google Scholar 

  63. Robyr D, Suka Y, Xenarios I, Kurdistani SK, Wang A, Suka N, Grunstein M (2002) Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell 109:437–446

    Article  PubMed  CAS  Google Scholar 

  64. Sabet N, Volo S, Yu C, Madigan JP, Morse RH (2004) Genome-wide analysis of the relationship between transcriptional regulation by Rpd3p and the histone H3 and H4 amino termini in budding yeast. Mol Cell Biol 24:8823–8833

    Article  PubMed  CAS  Google Scholar 

  65. Schmitt AP, McEntee K (1996) Msn2p, a zinc finger DNA-binding protein, is the transcriptional activator of the multistress response in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 93:5777–5782

    Article  PubMed  CAS  Google Scholar 

  66. Sheikh-Hamad D, Gustin MC (2004) MAP kinases and the adaptive response to hypertonicity: functional preservation from yeast to mammals. Am J Physiol Renal Physiol 287:F1102–F1110

    Article  PubMed  CAS  Google Scholar 

  67. Simone C, Forcales SV, Hill DA, Imbalzano AN, Latella L, Puri PL (2004) p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci. Nat Genet 36:738–743

    Article  PubMed  CAS  Google Scholar 

  68. Sims RJ III, Belotserkovskaya R, Reinberg D (2004) Elongation by RNA polymerase II: the short and long of it. Genes Dev 18:2437–2468

    Article  PubMed  CAS  Google Scholar 

  69. Soloaga A, Thomson S, Wiggin GR, Rampersaud N, Dyson MH, Hazzalin CA, Mahadevan LC, Arthur JS (2003) MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. EMBO J 22:2788–2797

    Article  PubMed  CAS  Google Scholar 

  70. Tatebayashi K, Yamamoto K, Tanaka K, Tomida T, Maruoka T, Kasukawa E, Saito H (2006) Adaptor functions of Cdc42, Ste50, and Sho1 in the yeast osmoregulatory HOG MAPK pathway. EMBO J 25:3033–3044

    Article  PubMed  CAS  Google Scholar 

  71. Truckses DM, Bloomekatz JE, Thorner J (2006) The RA domain of Ste50 adaptor protein is required for delivery of Ste11 to the plasma membrane in the filamentous growth signaling pathway of the yeast Saccharomyces cerevisiae. Mol Cell Biol 26:912–928

    Article  PubMed  CAS  Google Scholar 

  72. Vasudevan S, Garneau N, Tu KD, Peltz SW (2005) p38 mitogen-activated protein kinase/Hog1p regulates translation of the AU-rich-element-bearing MFA2 transcript. Mol Cell Biol 25:9753–9763

    Article  PubMed  CAS  Google Scholar 

  73. Vasudevan S, Peltz SW (2001) Regulated ARE-mediated mRNA decay in Saccharomyces cerevisiae. Mol Cell 7:1191–1200

    Article  PubMed  CAS  Google Scholar 

  74. Vincent AC, Struhl K (1992) ACR1, a yeast ATF/CREB repressor. Mol Cell Biol 12:5394–5405

    PubMed  CAS  Google Scholar 

  75. Wang A, Kurdistani SK, Grunstein M (2002) Requirement of Hos2 histone deacetylase for gene activity in yeast. Science 298:1412–1414

    Article  PubMed  CAS  Google Scholar 

  76. Warmka J, Hanneman J, Lee J, Amin D, Ota I (2001) Ptc1, a type 2C Ser/Thr phosphatase, inactivates the HOG pathway by dephosphorylating the mitogen-activated protein kinase Hog1. Mol Cell Biol 21:51–60

    Article  PubMed  CAS  Google Scholar 

  77. Westfall PJ, Ballon DR, Thorner J (2004) When the stress of your environment makes you go HOG wild. Science 306:1511–1512

    Article  PubMed  CAS  Google Scholar 

  78. Winters MJ, Pryciak PM (2005) Interaction with the SH3 domain protein Bem1 regulates signaling by the Saccharomyces cerevisiae p21-activated kinase Ste20. Mol Cell Biol 25:2177–2190

    Article  PubMed  CAS  Google Scholar 

  79. Wurgler-Murphy SM, Maeda T, Witten EA, Saito H (1997). Regulation of the Saccharomyces cerevisiae HOG1 mitogen-activated protein kinase by the PTP2 and PTP3 protein tyrosine phosphatases. Mol Cell Biol 17:1289–1297

    PubMed  CAS  Google Scholar 

  80. Yu YT, Breitbart RE, Smoot LB, Lee Y, Mahdavi V, Nadal-Ginard B (1992) Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev 6:1783–1798

    Article  PubMed  CAS  Google Scholar 

  81. Zarrinpar A, Bhattacharyya RP, Nittler MP, Lim WA (2004) Sho1 and Pbs2 act as coscaffolds linking components in the yeast high osmolarity MAP kinase pathway. Mol Cell 14:825–832

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain

    Eulàlia de Nadal & Francesc Posas

Authors
  1. Eulàlia de Nadal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesc Posas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesc Posas .

Editor information

Francesc Posas Angel R. Nebreda

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

de Nadal, E., Posas, F. (2007). Regulation of gene expression in response to osmostress by the yeast stress-activated protein kinase Hog1. 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_0244

Download citation

Publish with us

Policies and ethics

Search

Navigation