NameMitogen-activated protein kinase 1
Synonyms
  • 2.7.11.24
  • ERK-2
  • ERK2
  • ERT1
  • Extracellular signal-regulated kinase 2
  • MAP kinase 1
  • MAP kinase 2
  • MAP kinase isoform p42
  • MAPK 2
  • Mitogen-activated protein kinase 2
  • p42-MAPK
  • PRKM1
  • PRKM2
Gene NameMAPK1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001838|Mitogen-activated protein kinase 1
MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFE
HQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQH
LSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDH
TGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHI
LGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHK
RIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS
Number of residues360
Molecular Weight41389.265
Theoretical pI6.99
GO Classification
Functions
  • ATP binding
  • phosphatase binding
  • protein serine/threonine kinase activity
  • RNA polymerase II carboxy-terminal domain kinase activity
  • DNA binding
  • MAP kinase activity
Processes
  • toll-like receptor 4 signaling pathway
  • platelet activation
  • positive regulation of peptidyl-threonine phosphorylation
  • fibroblast growth factor receptor signaling pathway
  • ERK1 and ERK2 cascade
  • toll-like receptor 5 signaling pathway
  • transcription, DNA-templated
  • positive regulation of telomerase activity
  • insulin receptor signaling pathway
  • MAPK cascade
  • B cell receptor signaling pathway
  • toll-like receptor 9 signaling pathway
  • activation of MAPK activity
  • positive regulation of telomere capping
  • signal transduction
  • neurotrophin TRK receptor signaling pathway
  • toll-like receptor signaling pathway
  • peptidyl-threonine phosphorylation
  • positive regulation of telomere maintenance via telomerase
  • protein phosphorylation
  • toll-like receptor TLR1
  • T cell receptor signaling pathway
  • regulation of cellular response to heat
  • Ras protein signal transduction
  • toll-like receptor TLR6
  • axon guidance
  • peptidyl-serine phosphorylation
  • regulation of cytoskeleton organization
  • vascular endothelial growth factor receptor signaling pathway
  • caveolin-mediated endocytosis
  • trachea formation
  • cellular response to DNA damage stimulus
  • regulation of early endosome to late endosome transport
  • blood coagulation
  • labyrinthine layer blood vessel development
  • cellular response to granulocyte macrophage colony-stimulating factor stimulus
  • TRIF-dependent toll-like receptor signaling pathway
  • epidermal growth factor receptor signaling pathway
  • JAK-STAT cascade involved in growth hormone signaling pathway
  • regulation of Golgi inheritance
  • positive regulation of cell proliferation
  • cellular response to heat
  • Fc-gamma receptor signaling pathway involved in phagocytosis
  • regulation of protein stability
  • response to estrogen
  • cytosine metabolic process
  • innate immune response
  • regulation of sequence-specific DNA binding transcription factor activity
  • ERBB signaling pathway
  • Fc-epsilon receptor signaling pathway
  • response to epidermal growth factor
  • response to exogenous dsRNA
  • small GTPase mediated signal transduction
  • sensory perception of pain
  • lung morphogenesis
  • positive regulation of cell migration
  • viral process
  • stress-activated MAPK cascade
  • synaptic transmission
  • mammary gland epithelial cell proliferation
  • positive regulation of transcription, DNA-templated
  • toll-like receptor 10 signaling pathway
  • cell cycle
  • negative regulation of cell differentiation
  • MAPK import into nucleus
  • long-term synaptic potentiation
  • toll-like receptor 2 signaling pathway
  • chemotaxis
  • response to toxic substance
  • MyD88-dependent toll-like receptor signaling pathway
  • activation of MAPKK activity
  • positive regulation of translation
  • regulation of stress-activated MAPK cascade
  • toll-like receptor 3 signaling pathway
  • response to stress
  • lipopolysaccharide-mediated signaling pathway
  • MyD88-independent toll-like receptor signaling pathway
  • apoptotic process
Components
  • dendrite cytoplasm
  • focal adhesion
  • mitochondrion
  • Golgi apparatus
  • protein complex
  • cytosol
  • mitotic spindle
  • extracellular exosome
  • nucleoplasm
  • cytoskeleton
  • microtubule cytoskeleton
  • late endosome
  • nucleus
  • axon
  • perikaryon
  • early endosome
  • caveola
  • microtubule organizing center
  • pseudopodium
  • cytoplasm
General FunctionRna polymerase ii carboxy-terminal domain kinase activity
Specific FunctionSerine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation.Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID182191
UniProtKB IDP28482
UniProtKB Entry NameMK01_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0010648|Mitogen-activated protein kinase 1 (MAPK1)
ATGGCGGCGGCGGCGGCGGCGGGCGCGGGCCCGGAGATGGTCCGCGGGCAGGTGTTCGAC
GTGGGGCCGCGCTACACCAACCTCTCGTACATCGGCGAGGGCGCCTACGGCATGGTGTGC
TCTGCTTATGATAATGTCAACAAAGTTCGAGTAGCTATCAAGAAAATCAGCCCCTTTGAG
CACCAGACCTACTGCCAGAGAACCCTGAGGGAGATAAAAATCTTACTGCGCTTCAGACAT
GAGAACATCATTGGAATCAATGACATTATTCGAGCACCAACCATCGAGCAAATGAAAGAT
GTATATATAGTACAGGACCTCATGGAAACAGATCTTTACAAGCTCTTGAAGACACAACAC
CTCAGCAATGACCATATCTGCTATTTTCTCTACCAGATCCTCAGAGGGTTAAAATATATC
CATTCAGCTAACGTTCTGCACCGTGACCTCAAGCCTTCCAACCTGCTGCTCAACACCACC
TGTGATCTCAAGATCTGTGACTTTGGCCTGGCCCGTGTTGCAGATCCAGACCATGATCAC
ACAGGGTTCCTGACAGAATATGTGGCCACACGTTGGTACAGGGCTCCAGAAATTATGTTG
AATTCCAAGGGCTACACCAAGTCCATTGATATTTGGTCTGTAGGCTGCATTCTGGCAGAA
ATGCTTTCTAACAGGCCCATCTTTCCAGGGAAGCATTATCTTGACCAGCTGAACCACATT
TTGGGTATTCTTGGATCCCCATCACAAGAAGACCTGAATTGTATAATAAATTTAAAAGCT
AGGAACTATTTGCTTTCTCTTCCACACAAAAATAAGGTGCCATGGAACAGGCTGTTCCCA
AATGCTGACTCCAAAGCTCTGGACTTATTGGACAAAATGTTGACATTCAACCCACACAAG
AGGATTGAAGTAGAACAGGCTCTGGCCCACCCATATCTGGAGCAGTATTACGACCCGAGT
GACGAGCCCATCGCCGAAGCACCATTCAAGTTCGACATGGAATTGGATGACTTGCCTAAG
GAAAAGCTCAAAGAACTAATTTTTGAAGAGACTGCTAGATTCCAGCCAGGATACAGATCT
TAA
GenBank Gene IDM84489
GeneCard IDNot Available
GenAtlas IDMAPK1
HGNC IDHGNC:6871
Chromosome Location22
Locus22q11.2|22q11.21
References
  1. Owaki H, Makar R, Boulton TG, Cobb MH, Geppert TD: Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1416-22. 1540184
  2. Gonzalez FA, Raden DL, Rigby MR, Davis RJ: Heterogeneous expression of four MAP kinase isoforms in human tissues. FEBS Lett. 1992 Jun 15;304(2-3):170-8. 1319925
  3. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. 10591208
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. 12665801
  6. Sgouras DN, Athanasiou MA, Beal GJ Jr, Fisher RJ, Blair DG, Mavrothalassitis GJ: ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress ets-associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation. EMBO J. 1995 Oct 2;14(19):4781-93. 7588608
  7. Sithanandam G, Latif F, Duh FM, Bernal R, Smola U, Li H, Kuzmin I, Wixler V, Geil L, Shrestha S: 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region. Mol Cell Biol. 1996 Mar;16(3):868-76. 8622688
  8. Greenway A, Azad A, Mills J, McPhee D: Human immunodeficiency virus type 1 Nef binds directly to Lck and mitogen-activated protein kinase, inhibiting kinase activity. J Virol. 1996 Oct;70(10):6701-8. 8794306
  9. Ni H, Wang XS, Diener K, Yao Z: MAPKAPK5, a novel mitogen-activated protein kinase (MAPK)-activated protein kinase, is a substrate of the extracellular-regulated kinase (ERK) and p38 kinase. Biochem Biophys Res Commun. 1998 Feb 13;243(2):492-6. 9480836
  10. Deak M, Clifton AD, Lucocq LM, Alessi DR: Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 1998 Aug 3;17(15):4426-41. 9687510
  11. Niu H, Ye BH, Dalla-Favera R: Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes Dev. 1998 Jul 1;12(13):1953-61. 9649500
  12. Camps M, Nichols A, Gillieron C, Antonsson B, Muda M, Chabert C, Boschert U, Arkinstall S: Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase. Science. 1998 May 22;280(5367):1262-5. 9596579
  13. Todd JL, Tanner KG, Denu JM: Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway. J Biol Chem. 1999 May 7;274(19):13271-80. 10224087
  14. Cruzalegui FH, Cano E, Treisman R: ERK activation induces phosphorylation of Elk-1 at multiple S/T-P motifs to high stoichiometry. Oncogene. 1999 Dec 23;18(56):7948-57. 10637505
  15. Brondello JM, Pouyssegur J, McKenzie FR: Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation. Science. 1999 Dec 24;286(5449):2514-7. 10617468
  16. Scheper GC, Morrice NA, Kleijn M, Proud CG: The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells. Mol Cell Biol. 2001 Feb;21(3):743-54. 11154262
  17. Ouwens DM, de Ruiter ND, van der Zon GC, Carter AP, Schouten J, van der Burgt C, Kooistra K, Bos JL, Maassen JA, van Dam H: Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38. EMBO J. 2002 Jul 15;21(14):3782-93. 12110590
  18. Garcia J, Ye Y, Arranz V, Letourneux C, Pezeron G, Porteu F: IEX-1: a new ERK substrate involved in both ERK survival activity and ERK activation. EMBO J. 2002 Oct 1;21(19):5151-63. 12356731
  19. Sano H, Liu SC, Lane WS, Piletz JE, Lienhard GE: Insulin receptor substrate 4 associates with the protein IRAS. J Biol Chem. 2002 May 31;277(22):19439-47. Epub 2002 Mar 23. 11912194
  20. Wu Y, Chen Z, Ullrich A: EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2. Biol Chem. 2003 Aug;384(8):1215-26. 12974390
  21. Masuda K, Shima H, Katagiri C, Kikuchi K: Activation of ERK induces phosphorylation of MAPK phosphatase-7, a JNK specific phosphatase, at Ser-446. J Biol Chem. 2003 Aug 22;278(34):32448-56. Epub 2003 Jun 6. 12794087
  22. Allan LA, Morrice N, Brady S, Magee G, Pathak S, Clarke PR: Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK. Nat Cell Biol. 2003 Jul;5(7):647-54. 12792650
  23. Lou Y, Xie W, Zhang DF, Yao JH, Luo ZF, Wang YZ, Shi YY, Yao XB: Nek2A specifies the centrosomal localization of Erk2. Biochem Biophys Res Commun. 2004 Aug 20;321(2):495-501. 15358203
  24. Ronnstrand L: Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci. 2004 Oct;61(19-20):2535-48. 15526160
  25. Mitsushima M, Suwa A, Amachi T, Ueda K, Kioka N: Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin. J Biol Chem. 2004 Aug 13;279(33):34570-7. Epub 2004 Jun 7. 15184391
  26. Domina AM, Vrana JA, Gregory MA, Hann SR, Craig RW: MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol. Oncogene. 2004 Jul 8;23(31):5301-15. 15241487
  27. Langlais P, Wang C, Dong LQ, Carroll CA, Weintraub ST, Liu F: Phosphorylation of Grb10 by mitogen-activated protein kinase: identification of Ser150 and Ser476 of human Grb10zeta as major phosphorylation sites. Biochemistry. 2005 Jun 21;44(24):8890-7. 15952796
  28. Chen CH, Wang WJ, Kuo JC, Tsai HC, Lin JR, Chang ZF, Chen RH: Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK. EMBO J. 2005 Jan 26;24(2):294-304. Epub 2004 Dec 16. 15616583
  29. Hong JW, Ryu MS, Lim IK: Phosphorylation of serine 147 of tis21/BTG2/pc3 by p-Erk1/2 induces Pin-1 binding in cytoplasm and cell death. J Biol Chem. 2005 Jun 3;280(22):21256-63. Epub 2005 Mar 23. 15788397
  30. Dougherty MK, Muller J, Ritt DA, Zhou M, Zhou XZ, Copeland TD, Conrads TP, Veenstra TD, Lu KP, Morrison DK: Regulation of Raf-1 by direct feedback phosphorylation. Mol Cell. 2005 Jan 21;17(2):215-24. 15664191
  31. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  32. Fujishiro SH, Tanimura S, Mure S, Kashimoto Y, Watanabe K, Kohno M: ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA. Biochem Biophys Res Commun. 2008 Mar 28;368(1):162-7. doi: 10.1016/j.bbrc.2008.01.066. Epub 2008 Jan 22. 18211802
  33. Hu Y, Mivechi NF: Association and regulation of heat shock transcription factor 4b with both extracellular signal-regulated kinase mitogen-activated protein kinase and dual-specificity tyrosine phosphatase DUSP26. Mol Cell Biol. 2006 Apr;26(8):3282-94. 16581800
  34. Degoutin J, Vigny M, Gouzi JY: ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation. FEBS Lett. 2007 Feb 20;581(4):727-34. Epub 2007 Jan 25. 17274988
  35. Xu TR, Baillie GS, Bhari N, Houslay TM, Pitt AM, Adams DR, Kolch W, Houslay MD, Milligan G: Mutations of beta-arrestin 2 that limit self-association also interfere with interactions with the beta2-adrenoceptor and the ERK1/2 MAPKs: implications for beta2-adrenoceptor signalling via the ERK1/2 MAPKs. Biochem J. 2008 Jul 1;413(1):51-60. doi: 10.1042/BJ20080685. 18435604
  36. Zhong JL, Poghosyan Z, Pennington CJ, Scott X, Handsley MM, Warn A, Gavrilovic J, Honert K, Kruger A, Span PN, Sweep FC, Edwards DR: Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma. Mol Cancer Res. 2008 Mar;6(3):383-94. doi: 10.1158/1541-7786.MCR-07-2028. Epub 2008 Feb 22. 18296648
  37. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  38. Chuderland D, Konson A, Seger R: Identification and characterization of a general nuclear translocation signal in signaling proteins. Mol Cell. 2008 Sep 26;31(6):850-61. doi: 10.1016/j.molcel.2008.08.007. Epub 2008 Sep 4. 18760948
  39. Vomastek T, Iwanicki MP, Burack WR, Tiwari D, Kumar D, Parsons JT, Weber MJ, Nandicoori VK: Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction. Mol Cell Biol. 2008 Nov;28(22):6954-66. doi: 10.1128/MCB.00925-08. Epub 2008 Sep 15. 18794356
  40. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  41. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  42. Hu S, Xie Z, Onishi A, Yu X, Jiang L, Lin J, Rho HS, Woodard C, Wang H, Jeong JS, Long S, He X, Wade H, Blackshaw S, Qian J, Zhu H: Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell. 2009 Oct 30;139(3):610-22. doi: 10.1016/j.cell.2009.08.037. 19879846
  43. Sun J, Pedersen M, Ronnstrand L: The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction. J Biol Chem. 2009 Apr 24;284(17):11039-47. doi: 10.1074/jbc.M808058200. Epub 2009 Mar 5. 19265199
  44. Sacco F, Tinti M, Palma A, Ferrari E, Nardozza AP, Hooft van Huijsduijnen R, Takahashi T, Castagnoli L, Cesareni G: Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases. J Biol Chem. 2009 Aug 14;284(33):22048-58. doi: 10.1074/jbc.M109.002758. Epub 2009 Jun 3. 19494114
  45. Won M, Park KA, Byun HS, Kim YR, Choi BL, Hong JH, Park J, Seok JH, Lee YH, Cho CH, Song IS, Kim YK, Shen HM, Hur GM: Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration. J Hepatol. 2009 Jul;51(1):67-76. doi: 10.1016/j.jhep.2009.02.027. Epub 2009 Apr 16. 19447520
  46. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. 19369195
  47. Lorenz K, Schmitt JP, Schmitteckert EM, Lohse MJ: A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy. Nat Med. 2009 Jan;15(1):75-83. doi: 10.1038/nm.1893. Epub 2008 Dec 7. 19060905
  48. Yoon S, Seger R: The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors. 2006 Mar;24(1):21-44. 16393692
  49. Yao Z, Seger R: The ERK signaling cascade--views from different subcellular compartments. Biofactors. 2009 Sep-Oct;35(5):407-16. doi: 10.1002/biof.52. 19565474
  50. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  51. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  52. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  53. Wortzel I, Seger R: The ERK Cascade: Distinct Functions within Various Subcellular Organelles. Genes Cancer. 2011 Mar;2(3):195-209. doi: 10.1177/1947601911407328. 21779493
  54. Lim JH, Liu Y, Reineke E, Kao HY: Mitogen-activated protein kinase extracellular signal-regulated kinase 2 phosphorylates and promotes Pin1 protein-dependent promyelocytic leukemia protein turnover. J Biol Chem. 2011 Dec 30;286(52):44403-11. doi: 10.1074/jbc.M111.289512. Epub 2011 Oct 27. 22033920
  55. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  56. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. 22223895
  57. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  58. Reiterer V, Fey D, Kolch W, Kholodenko BN, Farhan H: Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2. Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):E2934-43. doi: 10.1073/pnas.1301985110. Epub 2013 Jul 11. 23847209
  59. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  60. Fox T, Coll JT, Xie X, Ford PJ, Germann UA, Porter MD, Pazhanisamy S, Fleming MA, Galullo V, Su MS, Wilson KP: A single amino acid substitution makes ERK2 susceptible to pyridinyl imidazole inhibitors of p38 MAP kinase. Protein Sci. 1998 Nov;7(11):2249-55. 9827991
  61. Ohori M, Kinoshita T, Okubo M, Sato K, Yamazaki A, Arakawa H, Nishimura S, Inamura N, Nakajima H, Neya M, Miyake H, Fujii T: Identification of a selective ERK inhibitor and structural determination of the inhibitor-ERK2 complex. Biochem Biophys Res Commun. 2005 Oct 14;336(1):357-63. 16139248
  62. Kinoshita T, Warizaya M, Ohori M, Sato K, Neya M, Fujii T: Crystal structure of human ERK2 complexed with a pyrazolo[3,4-c]pyridazine derivative. Bioorg Med Chem Lett. 2006 Jan 1;16(1):55-8. Epub 2005 Oct 18. 16242327
  63. Ohori M, Kinoshita T, Yoshimura S, Warizaya M, Nakajima H, Miyake H: Role of a cysteine residue in the active site of ERK and the MAPKK family. Biochem Biophys Res Commun. 2007 Feb 16;353(3):633-7. Epub 2006 Dec 20. 17194451
  64. Aronov AM, Baker C, Bemis GW, Cao J, Chen G, Ford PJ, Germann UA, Green J, Hale MR, Jacobs M, Janetka JW, Maltais F, Martinez-Botella G, Namchuk MN, Straub J, Tang Q, Xie X: Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors. J Med Chem. 2007 Mar 22;50(6):1280-7. Epub 2007 Feb 15. 17300186
  65. Critton DA, Tortajada A, Stetson G, Peti W, Page R: Structural basis of substrate recognition by hematopoietic tyrosine phosphatase. Biochemistry. 2008 Dec 16;47(50):13336-45. doi: 10.1021/bi801724n. 19053285
  66. Aronov AM, Tang Q, Martinez-Botella G, Bemis GW, Cao J, Chen G, Ewing NP, Ford PJ, Germann UA, Green J, Hale MR, Jacobs M, Janetka JW, Maltais F, Markland W, Namchuk MN, Nanthakumar S, Poondru S, Straub J, ter Haar E, Xie X: Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control. J Med Chem. 2009 Oct 22;52(20):6362-8. doi: 10.1021/jm900630q. 19827834