4,793
Views
945
CrossRef citations to date
0
Altmetric
Original

The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions

&
Pages 21-44 | Published online: 11 Jul 2009

References

  • Adachi M, Fukuda M, Nishida E. Nuclear export of MAP kinase (ERK) involves a MAP kinase kinase (MEK)-dependent active transport mechanism. J Cell Biol 2000; 148: 849–856
  • Adam LP, Hathaway DR. Identification of mitogen-activated protein kinase phosphorylation sequences in mammalian h-Caldesmon. FEBS Lett 1993; 322: 56–60
  • Adams JP, Anderson AE, Varga AW, Dineley KT, Cook RG, Pfaffinger PJ, Sweatt JD. The A-type potassium channel Kv4.2 is a substrate for the mitogen-activated protein kinase ERK. J Neurochem 2000; 75: 2277–2287
  • Aebersold DM, Shaul YD, Yung Y, Yarom N, Yao Z, Hanoch T, Seger R. Extracellular signal-regulated kinase 1c (ERK1c), a novel 42-kDa ERK, demonstrates unique modes of regulation, localization, and function. Mol Cell Biol 2004; 24: 10000–10015
  • Ahn NG, Seger R, Bratlien RL, Diltz CD, Tonks NK, Krebs EG. Multiple components in an epidermal growth factor-stimulated protein kinase cascade. In vitro activation of myelin basic protein/microtubule-associated protein-2 kinase. J Biol Chem 1991; 266: 4220–4227
  • 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; 5: 647–654
  • Alvarez E, Northwood IC, Gonzalez FA, Latour DA, Seth A, Abate C, Curran T, Davis RJ. Pro-Leu-Ser/Thr-Pro is a consensus primary sequence for substrate protein phosphorylation. Characterization of the phosphorylation of c-myc and c-jun proteins by an epidermal growth factor receptor threonine 669 protein kinase. J Biol Chem 1991; 266: 15277–15285
  • Anderson NG, Li P, Marsden LA, Williams N, Roberts TM, Sturgill TW. Raf-1 is a potential substrate for mitogen-activated protein kinase in vivo. Biochem J 1991; 277(Pt 2)573–576
  • Andreozzi F, D'Alessandris C, Federici M, Laratta E, Del Guerra S, Del Prato S, Marchetti P, Lauro R, Perticone F, Sesti G. Activation of the hexosamine pathway leads to phosphorylation of insulin receptor substrate-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin insulin biosynthetic pathway in RIN pancreatic beta-cells. Endocrinology 2004; 145: 2845–2857
  • Arnaud M, Crouin C, Deon C, Loyaux D, Bertoglio J. Phosphorylation of Grb2-associated binder 2 on serine 623 by ERK MAPK regulates its association with the phosphatase SHP-2 and decreases STAT5 activation. J Immunol 2004; 173: 3962–3971
  • Biswas SC, Greene LA. Nerve growth factor (NGF) down-regulates the Bcl-2 homology 3 (BH3) domain-only protein Bim and suppresses its proapoptotic activity by phosphorylation. J Biol Chem 2002; 277: 49511–49516
  • Bogoyevitch MA, Court NW. Counting on mitogen-activated protein kinases—ERKs 3, 4, 5, 6, 7 and 8. Cell Signal 2004; 16: 1345–1354
  • Boulton TG, Yancopoulos GD, Gregory JS, Slaughter C, Moomaw C, Hsu J, Cobb MH. An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science 1990; 249: 64–67
  • Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewska E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MH, Yancopoulos GD. ERK's: A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell 1991; 65: 663–675
  • Brondello JM, Pouyssegur J, McKenzie FR. Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation. Science 1999; 286: 2514–2517
  • Brown MC, Turner CE. Paxillin: Adapting to change. Physiol Rev 2004; 84: 1315–1339
  • Brummer T, Naegele H, Reth M, Misawa Y. Identification of novel ERK-mediated feedback phosphorylation sites at the C-terminus of B-Raf. Oncogene 2003; 22: 8823–8834
  • Buchwalter G, Gross C, Wasylyk B. Ets ternary complex transcription factors. Gene 2004; 324: 1–14
  • Buckley CT, Sekiya F, Kim YJ, Rhee SG, Caldwell KK. Identification of phospholipase C-gamma 1 as a mitogen-activated protein kinase substrate. J Biol Chem 2004; 279: 41807–41814
  • Cacace AM, Michaud NR, Therrien M, Mathes K, Copeland T, Rubin GM, Morrison DK. Identification of constitutive and ras-inducible phosphorylation sites of KSR: Implications for 14-3-3 binding, mitogen-activated protein kinase binding, and KSR overexpression. Mol Cell Biol 1999; 19: 229–240
  • 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; 280: 1262–1265
  • Canagarajah BJ, Khokhlatchev A, Cobb MH, Goldsmith EJ. Activation mechanism of the MAP kinase ERK2 by dual phosphorylation. Cell 1997; 90: 859–869
  • Chadee DN, Kyriakis JM. MLK3 is required for mitogen activation of B-Raf, ERK and cell proliferation. Nat Cell Biol 2004; 6: 770–776
  • Chang CI, Xu BE, Akella R, Cobb MH, Goldsmith EJ. Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b. Mol Cell 2002; 9: 1241–1249
  • Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B, Wright A, Vanderbilt C, Cobb MH. MAP kinases. Chem Rev 2001; 101: 2449–2476
  • 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; 24: 294–304
  • Cheng JT, Cobb MH, Baer R. Phosphorylation of the TAL1 oncoprotein by the extracellular-signal-regulated protein kinase ERK1. Mol Cell Biol 1993; 13: 801–808
  • Chevet E, Wong HN, Gerber D, Cochet C, Fazel A, Cameron PH, Gushue JN, Thomas DY, Bergeron JJ. Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes. EMBO J 1999; 18: 3655–3666
  • Chu B, Soncin F, Price BD, Stevenson MA, Calderwood SK. Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional activation by heat shock factor-1. J Biol Chem 1996; 271: 30847–30857
  • Chuderland D, Seger R. Protein–protein interactions in the regulation of the extracellular signal-regulated kinase. Mol Biotechnol 2005; 29: 57–74
  • Chung J, Uchida E, Grammer TC, Blenis J. STAT3 serine phosphorylation by ERK-dependent and -independent pathways negatively modulates its tyrosine phosphorylation. Mol Cell Biol 1997; 17: 6508–6516
  • Cormont M, Tanti JF, Zahraoui A, Van Obberghen E, Le Marchand-Brustel Y. Rab4 is phosphorylated by the insulin-activated extracellular-signal-regulated kinase ERK1. Eur J Biochem 1994; 219: 1081–1085
  • Cottin V, Van Linden A, Riches DW. Phosphorylation of tumor necrosis factor receptor CD120a (p55) by p42(mapk/erk2) induces changes in its subcellular localization. J Biol Chem 1999; 274: 32975–32987
  • Cruzalegui FH, Cano E, Treisman R. ERK activation induces phosphorylation of Elk-1 at multiple S/T-P motifs to high stoichiometry. Oncogene 1999; 18: 7948–7957
  • Dalby KN, Morrice N, Caudwell FB, Avruch J, Cohen P. Identification of regulatory phosphorylation sites in MAPK-activated protein kinase-1a/p90rsk that are inducible by MAPK. J Biol Chem 1998; 273: 1496–1505
  • 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; 17: 4426–4441
  • Dhillon AS, Kolch W. Untying the regulation of the Raf-1 kinase. Arch Biochem Biophys 2002; 404: 3–9
  • 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; 23: 5301–5315
  • 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; 17: 215–224
  • Drewes G, Lichtenberg-Kraag B, Doring F, Mandelkow EM, Biernat J, Goris J, Doree M, Mandelkow E. Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state. EMBO J 1992; 11: 2131–2138
  • Eblen ST, Catling AD, Assanah MC, Weber MJ. Biochemical and biological functions of the N-terminal, noncatalytic domain of extracellular signal-regulated kinase 2. Mol Cell Biol 2001; 21: 249–259
  • Eblen ST, Kumar NV, Shah K, Henderson MJ, Watts CK, Shokat KM, Weber MJ. Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs. J Biol Chem 2003; 278: 14926–14935
  • Eferl R, Wagner EF. AP-1: A double-edged sword in tumorigenesis. Nat Rev Cancer 2003; 3: 859–868
  • Erickson AK, Payne DM, Martino PA, Rossomando AJ, Shabanowitz J, Weber MJ, Hunt DF, Sturgill TW. Identification by mass spectrometry of threonine 97 in bovine myelin basic protein as a specific phosphorylation site for mitogen-activated protein kinase. J Biol Chem 1990; 265: 19728–19735
  • Erikson RJ. Structure, expression, and regulation of protein kinases involved in the phosphorylation of ribosomal protain S6. J Biol Chem 1991; 266: 6007–6010
  • Fantz DA, Jacobs D, Glossip D, Kornfeld K. Docking sites on substrate proteins direct extracellular signal-regulated kinase to phosphorylate specific residues. J Biol Chem 2001; 276: 27256–27265
  • Felton-Edkins ZA, Fairley JA, Graham EL, Johnston IM, White RJ, Scott PH. The mitogen-activated protein (MAP) kinase ERK induces tRNA synthesis by phosphorylating TFIIIB. EMBO J 2003; 22: 2422–2432
  • Frodin M, Gammeltoft S. Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol 1999; 151: 65–77
  • Frodin M, Jensen CJ, Merienne K, Gammeltoft S. A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1. EMBO J 2000; 19: 2924–2934
  • Fukuda M, Gotoh I, Adachi M, Gotoh Y, Nishida E. A novel regulatory mechanism in the mitogen-activated protein (MAP) kinase cascade. Role of nuclear export signal of MAP kinase kinase. J Biol Chem 1997; 272: 32642–32648
  • Fukuda M, Gotoh I, Gotoh Y, Nishida E. Cytoplasmic localization of mitogen-activated protein kinase kinase directed by its NH2-terminal, leucine-rich short amino acid sequence, which acts as a nuclear export signal. J Biol Chem 1996; 271: 20024–20028
  • Fukunaga R, Hunter T. MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates. EMBO J 1997; 16: 1921–1933
  • Futter M, Uematsu K, Bullock SA, Kim Y, Hemmings HC, Jr, Nishi A, Greengard P, Nairn AC. Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5). Proc Natl Acad Sci USA 2005; 102: 3489–3494
  • 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; 21: 5151–5163
  • Garnovskaya MN, Mukhin YV, Vlasova TM, Grewal JS, Ullian ME, Tholanikunnel BG, Raymond JR. Mitogen-induced rapid phosphorylation of serine 795 of the retinoblastoma gene product in vascular smooth muscle cells involves ERK activation. J Biol Chem 2004; 279: 24899–24905
  • Gille H, Sharrocks AD, Shaw PE. Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature 1992; 358: 414–417
  • Glading A, Bodnar RJ, Reynolds IJ, Shiraha H, Satish L, Potter DA, Blair HC, Wells A. Epidermal growth factor activates m-calpain (calpain II), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation. Mol Cell Biol 2004; 24: 2499–2512
  • Gomez N, Cohen P. Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature 1991; 353: 170–173
  • Gonzalez FA, Raden DL, Davis RJ. Identification of substrate recognition determinants for human ERK1 and 2 protein kinases. J Biol Chem 1991; 266: 22159–22163
  • Gonzalez FA, Raden DL, Rigby MR, Davis RJ. Heterogeneous expression of four MAP kinase isoforms in human tissues. FEBS Lett 1992; 304: 170–178
  • Gotoh Y, Nishida E. Activation mechanism and function of the MAP kinase cascade. Mol Reprod Dev 1995; 42: 486–492
  • Gotoh I, Adachi M, Nishida E. Identification and characterization of a novel MAP kinase kinase kinase, MLTK. J Biol Chem 2001; 276: 4276–4286
  • Graves LM, Guy HI, Kozlowski P, Huang M, Lazarowski E, Pope RM, Collins MA, Dahlstrand EN, Earp HS, III, Evans DR. Regulation of carbamoyl phosphate synthetase by MAP kinase. Nature 2000; 403: 328–332
  • Habelhah H, Shah K, Huang L, Ostareck-Lederer A, Burlingame AL, Shokat KM, Hentze MW, Ronai Z. ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of translation. Nat Cell Biol 2001; 3: 325–330
  • Hagemann C, Rapp UR. Isotype-specific functions of Raf kinases. Exp Cell Res 1999; 253: 34–46
  • Hanlon M, Sturgill TW, Sealy L. ERK2- and p90(Rsk2)-dependent pathways regulate the CCAAT/enhancer-binding protein-beta interaction with serum response factor. J Biol Chem 2001; 276: 38449–38456
  • Haycock JW, Ahn NG, Cobb MH, Krebs EG. ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the phosphorylation of tyrosine hydroxylase at serine-31 in situ. Proc Natl Acad Sci USA 1992; 89: 2365–2369
  • Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev 2004; 18: 2195–2224
  • Haystead TA, Haystead CM, Hu C, Lin TA, Lawrence JC, Jr. Phosphorylation of PHAS-I by mitogen-activated protein (MAP) kinase. Identification of a site phosphorylated by MAP kinase in vitro and in response to insulin in rat adipocytes. J Biol Chem 1994; 269: 23185–23191
  • Hirai S, Katoh M, Terada M, Kyriakis JM, Zon LI, Rana A, Avruch J, Ohno S. MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase. J Biol Chem 1997; 272: 15167–15173
  • Hoffmann R, Baillie GS, MacKenzie SJ, Yarwood SJ, Houslay MD. The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. EMBO J 1999; 18: 893–903
  • Holland PM, Cooper JA. Protein modification: Docking sites for kinases. Curr Biol 1999; 9: R329–R331
  • Hong JW, Ryu MS, Lim IK. Phosphorylation of Ser147 of TIS21/BTG2/PC3 by p-Erk1/2 induces pin-1 binding in cytoplasm and cell death. J Biol Chem 2005
  • Hoshi M, Ohta K, Gotoh Y, Mori A, Murofushi H, Sakai H, Nishida E. Mitogen-activated-protein-kinase-catalyzed phosphorylation of microtubule-associated proteins, microtubule-associated protein 2 and microtubule-associated protein 4, induces an alteration in their function. Eur J Biochem 1992; 203: 43–52
  • Hu E, Kim JB, Sarraf P, Spiegelman BM. Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma. Science 1996; 274: 2100–2103
  • Hu Y, Wang X, Zeng L, Cai DY, Sabapathy K, Goff SP, Firpo EJ, Li B. ERK Phosphorylates p66shcA on Ser36 and Subsequently Regulates p27kip1 Expression via the Akt-FOXO3a Pathway: Implication of p27kip1 in Cell Response to Oxidative Stress. Mol Biol Cell 2005; 1: 1
  • Hunger-Glaser I, Salazar EP, Sinnett-Smith J, Rozengurt E. Bombesin, lysophosphatidic acid, and epidermal growth factor rapidly stimulate focal adhesion kinase phosphorylation at Ser-910: Requirement for ERK activation. J Biol Chem 2003; 278: 22631–22643
  • Ishibe S, Joly D, Zhu X, Cantley LG. Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol Cell 2003; 12: 1275–1285
  • Ishibe S, Joly D, Liu ZX, Cantley LG. Paxillin serves as an ERK-regulated scaffold for coordinating FAK and Rac activation in epithelial morphogenesis. Mol Cell 2004; 16: 257–267
  • Jaaro H, Rubinfeld H, Hanoch T, Seger R. Nuclear translocation of mitogen-activated protein kinase kinase (MEK1) in response to mitogenic stimulation. Proc Natl Acad Sci USA 1997; 94: 3742–3747
  • Jacobs D, Glossip D, Xing H, Muslin AJ, Kornfeld K. Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. Genes Dev 1999; 13: 163–175
  • Janknecht R. Analysis of the ERK-stimulated ETS transcription factor ER81. Mol Cell Biol 1996; 16: 1550–1556
  • Janknecht R, Nordheim A. MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP. Biochem Biophys Res Commun 1996; 228: 831–837
  • Janknecht R, Ernst WH, Nordheim A. SAP1a is a nuclear target of signaling cascades involving ERKs. Oncogene 1995; 10: 1209–1216
  • Jesch SA, Lewis TS, Ahn NG, Linstedt AD. Mitotic phosphorylation of Golgi reassembly stacking protein 55 by mitogen-activated protein kinase ERK2. Mol Biol Cell 2001; 12: 1811–1817
  • Jovanovic JN, Benfenati F, Siow YL, Sihra TS, Sanghera JS, Pelech SL, Greengard P, Czernik AJ. Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions. Proc Natl Acad Sci USA 1996; 93: 3679–3683
  • Kanemitsu MY, Lau AF. Epidermal growth factor stimulates the disruption of gap junctional communication and connexin43 phosphorylation independent of 12-0-tetradecanoylphorbol 13-acetate-sensitive protein kinase C: The possible involvement of mitogen-activated protein kinase. Mol Biol Cell 1993; 4: 837–848
  • Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 1995; 270: 1491–1494
  • Kato K, Ito H, Kamei K, Inaguma Y, Iwamoto I, Saga S. Phosphorylation of alphaB-crystallin in mitotic cells and identification of enzymatic activities responsible for phosphorylation. J Biol Chem 1998; 273: 28346–28354
  • Kawada M, Yamagoe S, Murakami Y, Suzuki K, Mizuno S, Uehara Y. Induction of p27Kip1 degradation and anchorage independence by Ras through the MAP kinase signaling pathway. Oncogene 1997; 15: 629–637
  • Kim DW, Cochran BH. Extracellular signal-regulated kinase binds to TFII-I and regulates its activation of the c-fos promoter. Mol Cell Biol 2000; 20: 1140–1148
  • Kim D, Dan HC, Park S, Yang L, Liu Q, Kaneko S, Ning J, He L, Yang H, Sun M, Nicosia SV, Cheng JQ. AKT/PKB signaling mechanisms in cancer and chemoresistance. Front Biosci 2005; 10: 975–984
  • Klemke RL, Cai S, Giannini AL, Gallagher PJ, de Lanerolle P, Cheresh DA. Regulation of cell motility by mitogen-activated protein kinase. J Cell Biol 1997; 137: 481–492
  • Kolch W, Heidecker G, Kochs G, Hummel R, Vahidi H, Mischak H, Finkenzeller G, Marme D, Rapp UR. Protein kinase C alpha activates RAF-1 by direct phosphorylation. Nature 1993; 364: 249–252
  • Kotzka J, Muller-Wieland D, Roth G, Kremer L, Munck M, Schurmann S, Knebel B, Krone W. Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade. J Lipid Res 2000; 41: 99–108
  • Kretzschmar M, Doody J, Massague J. Opposing BMP and EGF signalling pathways converge on the TGF-beta family mediator Smad1. Nature 1997; 389: 618–622
  • Kretzschmar M, Doody J, Timokhina I, Massague J. A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras. Genes Dev 1999; 13: 804–816
  • Ku H, Meier KE. Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells. J Biol Chem 2000; 275: 11333–11340
  • Kyriakis JM, App H, Zhang FX, Banerjee P, Brautigan DL, Rapp UR, Avruch J. Raf-1 activates MAP kinase-kinase. Nature 1992; 358: 417–421
  • Lange CA, Shen T, Horwitz KB. Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome. Proc Natl Acad Sci USA 2000; 97: 1032–1037
  • Lange-Carter CA, Pleiman CM, Gardner AM, Blumer KJ, Johnson GL. A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science 1993; 260: 315–317
  • Langlais P, Wang C, Dong LQ, Carroll CA, Weintraub ST, Liu F. Phosphorylation of grb10 by mitogen-activated protein kinase: Identification of ser(150) and ser(476) of human grb10zeta as major phosphorylation sites. Biochemistry 2005; 44: 8890–8897
  • Langlois WJ, Sasaoka T, Saltiel AR, Olefsky JM. Negative feedback regulation and desensitization of insulin- and epidermal growth factor-stimulated p21ras activation. J Biol Chem 1995; 270: 25320–25323
  • Lee T, Hoofnagle AN, Kabuyama Y, Stroud J, Min X, Goldsmith EJ, Chen L, Resing KA, Ahn NG. Docking motif interactions in MAP kinases revealed by hydrogen exchange mass spectrometry. Mol Cell 2004; 14: 43–55
  • Lefebvre C, Terret ME, Djiane A, Rassinier P, Maro B, Verlhac MH. Meiotic spindle stability depends on MAPK-interacting and spindle-stabilizing protein (MISS), a new MAPK substrate. J Cell Biol 2002; 157: 603–613
  • Lehr S, Kotzka J, Avci H, Sickmann A, Meyer HE, Herkner A, Muller-Wieland D. Identification of major ERK-related phosphorylation sites in Gab1. Biochemistry 2004; 43: 12133–12140
  • Lewis TS, Hunt JB, Aveline LD, Jonscher KR, Louie DF, Yeh JM, Nahreini TS, Resing KA, Ahn NG. Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. Mol Cell 2000; 6: 1343–1354
  • Lim CS, Kim SH, Jung JG, Kim JK, Song WK. Regulation of SPIN90 phosphorylation and interaction with Nck by ERK and cell adhesion. J Biol Chem 2003; 278: 52116–52123
  • Lin LL, Wartmann M, Lin AY, Knopf JL, Seth A, Davis RJ. cPLA2 is phosphorylated and activated by MAP kinase. Cell 1993; 72: 269–278
  • Liu ZX, Yu CF, Nickel C, Thomas S, Cantley LG. Hepatocyte growth factor induces ERK-dependent paxillin phosphorylation and regulates paxillin-focal adhesion kinase association. J Biol Chem 2002; 277: 10452–10458
  • Lo RS, Wotton D, Massague J. Epidermal growth factor signaling via Ras controls the Smad transcriptional co-repressor TGIF. EMBO J 2001; 20: 128–136
  • Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk: Implications for tuberous sclerosis and cancer pathogenesis. Cell 2005; 121: 179–193
  • MacGillivray MK, Cruz TF, McCulloch CA. The recruitment of the interleukin-1 (IL-1) receptor-associated kinase (IRAK) into focal adhesion complexes is required for IL-1beta -induced ERK activation. J Biol Chem 2000; 275: 23509–23515
  • MacKenzie SJ, Baillie GS, McPhee I, Bolger GB, Houslay MD. ERK2 mitogen-activated protein kinase binding, phosphorylation, and regulation of the PDE4D cAMP-specific phosphodiesterases. The involvement of COOH-terminal docking sites and NH2-terminal UCR regions. J Biol Chem 2000; 275: 16609–16617
  • Maekawa M, Nishida E, Tanoue T. Identification of the anti-proliferative protein Tob as a MAPK substrate. J Biol Chem 2002; 277: 37783–37787
  • Majumdar M, Meenakshi J, Goswami SK, Datta K. Hyaluronan binding protein 1 (HABP1)/C1QBP/p32 is an endogenous substrate for MAP kinase and is translocated to the nucleus upon mitogenic stimulation. Biochem Biophys Res Commun 2002; 291: 829–837
  • Manabe A, Iguchi-Ariga SM, Iizuka H, Ariga H. Transcriptional repression activity of N-MYC protein requires phosphorylation by MAP kinase. Biochem Biophys Res Commun 1996; 219: 813–823
  • Marais R, Wynne J, Treisman R. The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell 1993; 73: 381–393
  • Marchetti S, Gimond C, Chambard JC, Touboul T, Roux D, Pouyssegur J, Pages G. ERKs phosphorylate MAPK phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation. Mol Cell Biol 2005; 25: 854–864
  • Marklund U, Brattsand G, Shingler V, Gullberg M. Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase. J Biol Chem 1993; 268: 15039–15047
  • Markowitz RB, Hermann AS, Taylor DF, He L, Anthony-Cahill S, Ahn NG, Dynan WS. Phosphorylation of the C-terminal domain of RNA polymerase II by the extracellular-signal-regulated protein kinase ERK2. Biochem Biophys Res Commun 1995; 207: 1051–1057
  • Martinez-Quiles N, Ho HY, Kirschner MW, Ramesh N, Geha RS. Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP. Mol Cell Biol 2004; 24: 5269–5280
  • 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; 278: 32448–32456
  • Matheny SA, Chen C, Kortum RL, Razidlo GL, Lewis RE, White MA. Ras regulates assembly of mitogenic signalling complexes through the effector protein IMP. Nature 2004; 427: 256–260
  • Matsuda S, Gotoh Y, Nishida E. Phosphorylation of Xenopus mitogen-activated protein (MAP) kinase kinase by MAP kinase kinase kinase and MAP kinase. J Biol Chem 1993; 268: 3277–3281
  • Matsuda S, Miwa Y, Hirata Y, Minowa A, Tanaka J, Nishida E, Koyasu S. Negative feedback loop in T-cell activation through MAPK-catalyzed threonine phosphorylation of LAT. EMBO J 2004; 23: 2577–2585
  • McLaughlin MM, Kumar S, McDonnell PC, Van Horn S, Lee JC, Livi GP, Young PR. Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase. J Biol Chem 1996; 271: 8488–8492
  • Merchant JL, Du M, Todisco A. Sp1 phosphorylation by Erk 2 stimulates DNA binding. Biochem Biophys Res Commun 1999; 254: 454–461
  • Mikkola I, Bruun JA, Bjorkoy G, Holm T, Johansen T. Phosphorylation of the transactivation domain of Pax6 by extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. J Biol Chem 1999; 274: 15115–15126
  • Milanini-Mongiat J, Pouyssegur J, Pages G. Identification of two Sp1 phosphorylation sites for p42/p44 mitogen-activated protein kinases: Their implication in vascular endothelial growth factor gene transcription. J Biol Chem 2002; 277: 20631–20639
  • Milne DM, Campbell DG, Caudwell FB, Meek DW. Phosphorylation of the tumor suppressor protein p53 by mitogen-activated protein kinases. J Biol Chem 1994; 269: 9253–9260
  • 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; 279: 34570–34577
  • Mizutani A, Tokumitsu H, Kobayashi R, Hidaka H. Phosphorylation of annexin XI (CAP-50) in SR-3Y1 cells. J Biol Chem 1993; 268: 15517–15522
  • Morrison DK. KSR: A MAPK scaffold of the Ras pathway?. J Cell Sci 2001; 114: 1609–1612
  • Morrison DK, Davis RJ. Regulation of MAP kinase signaling modules by scaffold proteins in mammals. Annu Rev Cell Dev Biol 2003; 19: 91–118
  • Morton S, Davis RJ, McLaren A, Cohen P. A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. EMBO J 2003; 22: 3876–3886
  • Mukhopadhyay NK, Price DJ, Kyriakis JM, Pelech S, Sanghera J, Avruch J. An array of insulin-activated, proline-directed serine/threonine protein kinases phosphorylate the p70 S6 kinase. J Biol Chem 1992; 267: 3325–3335
  • Murphy LO, Smith S, Chen RH, Fingar DC, Blenis J. Molecular interpretation of ERK signal duration by immediate early gene products. Nat Cell Biol 2002; 4: 556–564
  • Murphy LO, MacKeigan JP, Blenis J. A network of immediate early gene products propagates subtle differences in mitogen-activated protein kinase signal amplitude and duration. Mol Cell Biol 2004; 24: 144–153
  • Nakajima T, Kinoshita S, Sasagawa T, Sasaki K, Naruto M, Kishimoto T, Akira S. Phosphorylation at threonine-235 by a ras-dependent mitogen-activated protein kinase cascade is essential for transcription factor NF-IL6. Proc Natl Acad Sci USA 1993; 90: 2207–2211
  • Nemenoff RA, Winitz S, Qian NX, Van Putten V, Johnson GL, Heasley LE. Phosphorylation and activation of a high molecular weight form of phospholipase A2 by p42 microtubule-associated protein 2 kinase and protein kinase C. J Biol Chem 1993; 268: 1960–1964
  • 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; 243: 492–496
  • Nie L, Xu M, Vladimirova A, Sun XH. Notch-induced E2A ubiquitination and degradation are controlled by MAP kinase activities. EMBO J 2003; 22: 5780–5792
  • 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; 12: 1953–1961
  • Northwood IC, Gonzalez FA, Wartmann M, Raden DL, Davis RJ. Isolation and characterization of two growth factor-stimulated protein kinases that phosphorylate the epidermal growth factor receptor at threonine 669. J Biol Chem 1991; 266: 15266–15276
  • Ogier-Denis E, Pattingre S, El Benna J, Codogno P. Erk1/2-dependent phosphorylation of Galpha-interacting protein stimulates its GTPase accelerating activity and autophagy in human colon cancer cells. J Biol Chem 2000; 275: 39090–39095
  • 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; 21: 3782–3793
  • Palmer A, Gavin AC, Nebreda AR. A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1. EMBO J 1998; 17: 5037–5047
  • Payne DM, Rossomando AJ, Martino P, Erickson AK, Her J-H, Shabanowitz J, Hunt DF, Weber MJ, Sturgill TW. Identification of the regulatory phosphorylation sites in pp42/MAPK. EMBO J. 1991; 10: 885–892
  • Peraldi P, Zhao Z, Filloux C, Fischer EH, Van Obberghen E. Protein-tyrosine-phosphatase 2C is phosphorylated and inhibited by 44-kDa mitogen-activated protein kinase. Proc Natl Acad Sci U S A 1994; 91: 5002–5006
  • Perlson E, Hanz S, Ben-Yaakov K, Segal-Ruder Y, Seger R, Fainzilber M. Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve. Neuron 2005; 45: 715–726
  • Peter M, Sanghera JS, Pelech SL, Nigg EA. Mitogen-activated protein kinases phosphorylate nuclear lamins and display sequence specificity overlapping that of mitotic protein kinase p34cdc2. Eur J Biochem 1992; 205: 287–294
  • Pircher TJ, Petersen H, Gustafsson JA, Haldosen LA. Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a. Mol Endocrinol 1999; 13: 555–565
  • Pitcher JA, Tesmer JJ, Freeman JL, Capel WD, Stone WC, Lefkowitz RJ. Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases. J Biol Chem 1999; 274: 34531–34534
  • Pouyssegur J, Volmat V, Lenormand P. Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling. Biochem Pharmacol 2002; 64: 755–763
  • Price MA, Rogers AE, Treisman R. Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET). EMBO J 1995; 14: 2589–2601
  • Rajendra Kumar P, Singhal PK, Subba Rao MR, Mahalingam S. Phosphorylation by MAPK regulates simian immunodeficiency virus Vpx protein nuclear import and virus infectivity. J Biol Chem 2005; 280: 8553–8563
  • Ray LB, Sturgill TW. Characterization of insulin-stimulated microtubule-associated protein kinase. Rapid isolation and stabilization of a novel serine/threonine kinase from 3T3-L1 cells. Proc Natl Acad Sci USA 1987; 84: 1502–1506
  • Reszka AA, Seger R, Diltz CD, Krebs EG, Fischer EH. Association of mitogen-activated protein kinase with the microtubule cytoskeleton. Proc Natl Acad Sci USA 1995; 92: 8881–8885
  • Richard DE, Berra E, Gothie E, Roux D, Pouyssegur J. p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1. J Biol Chem 1999; 274: 32631–32637
  • Robinson FL, Whitehurst AW, Raman M, Cobb MH. Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1. J Biol Chem 2002; 277: 14844–14852
  • Roelen BA, Cohen OS, Raychowdhury MK, Chadee DN, Zhang Y, Kyriakis JM, Alessandrini AA, Lin HY. Phosphorylation of threonine 276 in Smad4 is involved in transforming growth factor-beta-induced nuclear accumulation. Am J Physiol Cell Physiol 2003; 285: C823–C830
  • Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: A family of kinases with diverse biological functions. Microbiol Mol Biol Rev 2004; 68: 320–344
  • Roux PP, Richards SA, Blenis J. Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity. Mol Cell Biol 2003; 23: 4796–4804
  • Rowan BG, Weigel NL, O'Malley BW. Phosphorylation of steroid receptor coactivator-1. Identification of the phosphorylation sites and phosphorylation through the mitogen-activated protein kinase pathway. J Biol Chem 2000; 275: 4475–4483
  • Rubinfeld H, Seger R. The ERK cascade as a prototype of MAPK signaling pathways. Methods Mol Biol 2004; 250: 1–28
  • Rubinfeld H, Hanoch T, Seger R. Identification of a cytoplasmic-retention sequence in ERK2. J Biol Chem 1999; 274: 30349–30352
  • Rui L, Herrington J, Carter-Su C. SH2-B, a membrane-associated adapter, is phosphorylated on multiple serines/threonines in response to nerve growth factor by kinases within the MEK/ERK cascade. J Biol Chem 1999; 274: 26485–26492
  • Sabio G, Reuver S, Feijoo C, Hasegawa M, Thomas GM, Centeno F, Kuhlendahl S, Leal-Ortiz S, Goedert M, Garner C, et al. Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2. Biochem J 2004; 380: 19–30
  • Salmeron A, Ahmad TB, Carlile GW, Pappin D, Narsimhan RP, Ley SC. Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase. EMBO J 1996; 15: 817–826
  • Sanada K, Okano T, Fukada Y. Mitogen-activated protein kinase phosphorylates and negatively regulates basic helix-loop-helix-PAS transcription factor BMAL1. J Biol Chem 2002; 277: 267–271
  • Sanada K, Harada Y, Sakai M, Todo T, Fukada Y. Serine phosphorylation of mCRY1 and mCRY2 by mitogen-activated protein kinase. Genes Cells 2004; 9: 697–708
  • Sano M. Chromatographic resolution and characterization of a nerve growth factor-dependent kinase that phosphorylates microtubule-associated proteins 1 and 2 in PC12 cells. J Neurochem 1992; 59: 1263–1272
  • Schaeffer HJ, Catling AD, Eblen ST, Collier LS, Krauss A, Weber MJ. MP1: A MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. Science 1998; 281: 1668–1671
  • Scheid MP, Schubert KM, Duronio V. Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase. J Biol Chem 1999; 274: 31108–31113
  • Schiemann WP, Graves LM, Baumann H, Morella KK, Gearing DP, Nielsen MD, Krebs EG, Nathanson NM. Phosphorylation of the human leukemia inhibitory factor (LIF) receptor by mitogen-activated protein kinase and the regulation of LIF receptor function by heterologous receptor activation. Proc Natl Acad Sci USA 1995; 92: 5361–5365
  • Schonwasser DC, Palmer RH, Herget T, Parker PJ. p42 MAPK phosphorylates 80 kDa MARCKS at Ser-113. FEBS Lett 1996; 395: 1–5
  • Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995; 9: 726–735
  • Seger R, Ahn NG, Boulton TG, Yancopoulos GD, Panayotatos N, Radziejewska E, Ericsson L, Bratlien RL, Cobb MH, Krebs EG. Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: Implication for their mechanism of activation. Proc Natl Acad Sci USA 1991; 88: 6142–6146
  • Seger R, Ahn NG, Posada J, Munar ES, Jensen AM, Cooper JA, Cobb MH, Krebs EG. Purification and characterization of MAP kinase activator(s) from epidermal growth factor stimulated A431 cells. J Biol Chem 1992a; 267: 14373–14381
  • Seger R, Seger D, Lozeman FJ, Ahn NG, Graves LM, Campbell JS, Ericsson L, Harrylock M, Jensen AM, Krebs EG. Human T-cell Map kinase kinases are related to yeast signal transduction kinases. J Biol Chem 1992b; 267: 25628–25631
  • 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; 14: 4781–4793
  • Shang WH, Adachi Y, Nakamura A, Copeland T, Kim SR, Kamata T. Regulation of amphiphysin1 by mitogen-activated protein kinase: Its significance in nerve growth factor receptor-mediated endocytosis. J Biol Chem 2004; 279: 40890–40896
  • Shapiro PS, Whalen AM, Tolwinski NS, Wilsbacher J, Froelich-Ammon SJ, Garcia M, Osheroff N, Ahn NG. Extracellular signal-regulated kinase activates topoisomerase IIalpha through a mechanism independent of phosphorylation. Mol Cell Biol 1999; 19: 3551–3560
  • Sharrocks AD, Yang SH, Galanis A. Docking domains and substrate-specificity determination for MAP kinases. Trends Biochem Sci 2000; 25: 448–453
  • Shemanko CS, Sanghera JS, Milner RE, Pelech S, Michalak M. Phosphorylation of the carboxyl terminal region of dystrophin by mitogen-activated protein (MAP) kinase. Mol Cell Biochem 1995; 152: 63–70
  • Shi H, Asher C, Chigaev A, Yung Y, Reuveny E, Seger R, Garty H. Interactions of beta and gamma ENaC with Nedd4 can be facilitated by an ERK-mediated phosphorylation. J Biol Chem 2002; 277: 13539–13547
  • Sif S, Stukenberg PT, Kirschner MW, Kingston RE. Mitotic inactivation of a human SWI/SNF chromatin remodeling complex. Genes Dev 1998; 12: 2842–2851
  • 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; 16: 868–876
  • Slagsvold HH, Ostvold AC, Fallgren AB, Paulsen RE. Nuclear receptor and apoptosis initiator NGFI-B is a substrate for kinase ERK2. Biochem Biophys Res Commun 2002; 291: 1146–1150
  • Songyang Z, Lu KP, Kwon YT, Tsai LH, Filhol O, Cochet C, Brickey DA, Soderling TR, Bartleson C, Graves DJ, et al. A structural basis for substrate specificities of protein Ser/Thr kinases: Primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1. Mol Cell Biol 1996; 16: 6486–6493
  • Standen CL, Perkinton MS, Byers HL, Kesavapany S, Lau KF, Ward M, McLoughlin D, Miller CC. The neuronal adaptor protein Fe65 is phosphorylated by mitogen-activated protein kinase (ERK1/2). Mol Cell Neurosci 2003; 24: 851–857
  • Stefanovsky VY, Pelletier G, Hannan R, Gagnon-Kugler T, Rothblum LI, Moss T. An immediate response of ribosomal transcription to growth factor stimulation in mammals is mediated by ERK phosphorylation of UBF. Mol Cell 2001; 8: 1063–1073
  • Sturgill TW, Ray LB. Muscle proteins related to microtubule associated protein-2 are substrates for an insulin-stimulatable kinase. Biochem Biophys Res Commun 1986; 134: 565–571
  • Sturgill TW, Ray LB, Erikson E, Maller JL. Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II. Nature 1988; 334: 715–718
  • Sundberg-Smith LJ, Doherty JT, Mack CP, Taylor JM. Adhesion stimulates direct PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. J Biol Chem 2005; 280: 2055–2064
  • Takekawa M, Tatebayashi K, Saito H. Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases. Mol Cell 2005; 18: 295–306
  • Tanaka T, Kurokawa M, Ueki K, Tanaka K, Imai Y, Mitani K, Okazaki K, Sagata N, Yazaki Y, Shibata Y, et al. The extracellular signal-regulated kinase pathway phosphorylates AML1, an acute myeloid leukemia gene product, and potentially regulates its transactivation ability. Mol Cell Biol 1996; 16: 3967–3979
  • Tanoue T, Nishida E. Molecular recognitions in the MAP kinase cascades. Cell Signal 2003; 15: 455–462
  • Tanoue T, Adachi M, Moriguchi T, Nishida E. A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nat Cell Biol 2000; 2: 110–116
  • Tanoue T, Maeda R, Adachi M, Nishida E. Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions. EMBO J 2001; 20: 466–479
  • Taylor GA, Thompson MJ, Lai WS, Blackshear PJ. Phosphorylation of tristetraprolin, a potential zinc finger transcription factor, by mitogen stimulation in intact cells and by MAPK in vitro. J Biol Chem 1995; 270: 13341–13347
  • Tee AR, Blenis J. mTOR, translational control and human disease. Semin Cell Dev Biol 2005; 16: 29–37
  • Terret ME, Lefebvre C, Djiane A, Rassinier P, Moreau J, Maro B, Verlhac MH. DOC1R: A MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes. Development 2003; 130: 5169–5177
  • Tohgo A, Pierce KL, Choy EW, Lefkowitz RJ, Luttrell LM. beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation. J Biol Chem 2002; 277: 9429–9436
  • Torii S, Kusakabe M, Yamamoto T, Maekawa M, Nishida E. Sef is a spatial regulator for Ras/MAP kinase signaling. Dev Cell 2004; 7: 33–44
  • Towatari M, Ciro M, Ottolenghi S, Tsuzuki S, Enver T. Involvement of mitogen-activated protein kinase in the cytokine-regulated phosphorylation of transcription factor GATA-1. Hematol J 2004; 5: 262–272
  • Treisman R. Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 1996; 8: 205–215
  • Uhlik MT, Abell AN, Cuevas BD, Nakamura K, Johnson GL. Wiring diagrams of MAPK regulation by MEKK1, 2, and 3. Biochem Cell Biol 2004; 82: 658–663
  • Veeranna, Amin ND, Ahn NG, Jaffe H, Winters CA, Grant P, Pant HC. Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys-Ser-Pro (KSP) repeats in neurofilament proteins NF-H and NF-M. J Neurosci 1998; 18: 4008–4021
  • Vomastek T, Schaeffer HJ, Tarcsafalvi A, Smolkin ME, Bissonette EA, Weber MJ. Modular construction of a signaling scaffold: MORG1 interacts with components of the ERK cascade and links ERK signaling to specific agonists. Proc Natl Acad Sci USA 2004; 101: 6981–6986
  • Wang QM, Guan KL, Roach PJ, DePaoli-Roach AA. Phosphorylation and activation of the ATP-Mg-dependent protein phosphatase by the mitogen-activated protein kinase. J Biol Chem 1995; 270: 18352–18358
  • Waskiewicz AJ, Flynn A, Proud CG, Cooper JA. Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J 1997; 16: 1909–1920
  • Weiler MC, Smith JL, Masters JN. CR16, a novel proline-rich protein expressed in rat brain neurons, binds to SH3 domains and is a MAP kinase substrate. J Mol Neurosci 1996; 7: 203–215
  • Wellbrock C, Karasarides M, Marais R. The RAF proteins take centre stage. Nat Rev Mol Cell Biol 2004; 5: 875–885
  • Whitmarsh AJ, Yang SH, Su MS, Sharrocks AD, Davis RJ. Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors. Mol Cell Biol 1997; 17: 2360–2371
  • Winkler DG, Park I, Kim T, Payne NS, Walsh CT, Strominger JL, Shin J. Phosphorylation of Ser-42 and Ser-59 in the N-terminal region of the tyrosine kinase p56lck. Proc Natl Acad Sci USA 1993; 90: 5176–5180
  • Wolf I, Rubinfeld H, Yoon S, Marmor G, Hanoch T, Seger R. Involvement of the activation loop of ERK in the detachment from cytosolic anchoring. J Biol Chem 2001; 276: 24490–24497
  • Wu M, Hemesath TJ, Takemoto CM, Horstmann MA, Wells AG, Price ER, Fisher D, Fisher DE. c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev 2000; 14: 301–312
  • Wu Y, Chen Z, Ullrich A. EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2. Biol Chem 2003; 384: 1215–1226
  • Xiao G, Jiang D, Thomas P, Benson MD, Guan K, Karsenty G, Franceschi RT. MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem 2000; 275: 4453–4459
  • Xing HR, Lozano J, Kolesnick R. Epidermal growth factor treatment enhances the kinase activity of kinase suppressor of Ras. J Biol Chem 2000; 275: 17276–17280
  • Xu Be B, Stippec S, Robinson F, Cobb MH. Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking. J Biol Chem 2001; 276: 26509–26515
  • Xu R, Seger R, Pecht I. Cutting edge: Extracellular signal-regulated kinase activates syk: A new potential feedback regulation of Fc epsilon receptor signaling. J Immunol 1999; 163: 1110–1114
  • Xu A, Suh PG, Marmy-Conus N, Pearson RB, Seok OY, Cocco L, Gilmour RS. Phosphorylation of nuclear PLCΦ1 by ERK mediates the mitogenic action of insulin-like growth factor I. Mol Cell Biol 2001; 21: 2981–2990
  • Yang X, Gabuzda D. Mitogen-activated protein kinase phosphorylates and regulates the HIV-1 Vif protein. J Biol Chem 1998; 273: 29879–29887
  • Yang TT, Xiong Q, Graef IA, Crabtree GR, Chow CW. Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex. Mol Cell Biol 2005; 25: 907–920
  • Yao Z, Seger R. The molecular Mechanism of MAPK/ERK inactivation. Curr Genom 2004; 5: 385–393
  • Yeh S, Lin HK, Kang HY, Thin TH, Lin MF, Chang C. From HER2/Neu signal cascade to androgen receptor and its coactivators: A novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Proc Natl Acad Sci USA 1999; 96: 5458–5463
  • Yeh PY, Chuang SE, Yeh KH, Song YC, Chang LL, Cheng AL. Phosphorylation of p53 on Thr55 by ERK2 is necessary for doxorubicin-induced p53 activation and cell death. Oncogene 2004; 23: 3580–3588
  • Yehia G, Schlotter F, Razavi R, Alessandrini A, Molina CA. Mitogen-activated protein kinase phosphorylates and targets inducible cAMP early repressor to ubiquitin-mediated destruction. J Biol Chem 2001; 276: 35272–35279
  • York RD, Yao H, Dillon T, Ellig CL, Eckert SP, McCleskey EW, Stork PJ. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 1998; 392: 622–626
  • Yoshimura S, Yoshioka K, Barr FA, Lowe M, Nakayama K, Ohkuma S, Nakamura N. Convergence of cell cycle regulation and growth factor signals on GRASP65. J Biol Chem 2005; 280: 23048–23056
  • Yoshioka K. Scaffold proteins in mammalian MAP kinase cascades. J Biochem (Tokyo) 2004; 135: 657–661
  • Young MR, Nair R, Bucheimer N, Tulsian P, Brown N, Chapp C, Hsu TC, Colburn NH. Transactivation of Fra-1 and consequent activation of AP-1 occur extracellular signal-regulated kinase dependently. Mol Cell Biol 2002; 22: 587–598
  • Yung Y, Yao Z, Hanoch T, Seger R. ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK. J Biol Chem 2000; 275: 15799–15808
  • Zecevic M, Catling AD, Eblen ST, Renzi L, Hittle JC, Yen TJ, Gorbsky GJ, Weber MJ. Active MAP kinase in mitosis: Localization at kinetochores and association with the motor protein CENP-E. J Cell Biol 1998; 142: 1547–1558
  • Zhang S, Fukushi M, Hashimoto S, Gao C, Huang L, Fukuyo Y, Nakajima T, Amagasa T, Enomoto S, Koike K, et al. A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling. Biochem Biophys Res Commun 2002; 297: 17–23
  • Zhang J, Zhou B, Zheng CF, Zhang ZY. A bipartite mechanism for ERK2 recognition by its cognate regulators and substrates. J Biol Chem 2003; 278: 29901–29912
  • Zhao J, Yuan X, Frodin M, Grummt I. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth. Mol Cell 2003; 11: 405–413
  • Zheng CF, Guan KL. Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases. J Biol Chem 1993; 268: 23933–23939
  • Zhong SP, Ma WY, Dong Z. ERKs and p38 kinases mediate ultraviolet B-induced phosphorylation of histone H3 at serine 10. J Biol Chem 2000; 275: 20980–20984
  • Zhou B, Zhang ZY. The activity of the extracellular signal-regulated kinase 2 is regulated by differential phosphorylation in the activation loop. J Biol Chem 2002; 277: 13889–13899
  • Zhou B, Wu L, Shen K, Zhang J, Lawrence DS, Zhang ZY. Multiple regions of MAP kinase phosphatase 3 are involved in its recognition and activation by ERK2. J Biol Chem 2001; 276: 6506–6515

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.