ERK2

Summary

Gene Symbol: ERK2
Description: mitogen-activated protein kinase 1
Alias: ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK, mitogen-activated protein kinase 1, MAP kinase 1, MAP kinase 2, MAP kinase isoform p42, MAPK 2, extracellular signal-regulated kinase 2, mitogen-activated protein kinase 2, protein tyrosine kinase ERK2
Species: human
Products:     ERK2

Top Publications

  1. Smith E, Cai K, Smedberg J, Ribeiro M, Rula M, Slater C, et al. Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells. PLoS ONE. 2010;5:e9295 pubmed publisher
    ..Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription...
  2. Kuo H, Hsu H, Chang C, Jiang M, Yeh C, Shen K, et al. High nuclear phosphorylated extracellular signal-regulated kinase expression associated with poor differentiation, larger tumor size, and an advanced stage of breast cancer. Pol J Pathol. 2013;64:163-9 pubmed
    ..018) of the disease. Thus, nuclear phosphorylated ERK1/2 is associated with enhanced proliferation and invasion of mammary carcinomas and may be a biomarker for breast cancer prognosis and the determination of therapeutic strategies. ..
  3. Dyugovskaya L, Polyakov A, Cohen Kaplan V, Lavie P, Lavie L. Bax/Mcl-1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: effects of p38MAPK and ERK1/2 signaling. J Transl Med. 2012;10:211 pubmed publisher
    ..IH induced ERK1/2 and p38MAPKs phosphorylation, whereas SH induced only p38MAPK phosphorylation. Accordingly, both ERK and p38MAPK inhibitors attenuated the IH-induced Mcl-1 increase...
  4. Li Z, Li C, Du L, Zhou Y, Wu W. Human chorionic gonadotropin ? induces migration and invasion via activating ERK1/2 and MMP-2 in human prostate cancer DU145 cells. PLoS ONE. 2013;8:e54592 pubmed publisher
    ..These results indicated that hCG? induced cell motility via promoting ERK1/2 phosphorylation and MMP-2 upregulation in human prostate cancer DU145 cells. ..
  5. Huang S, Liu F, Niu Q, Li Y, Liu C, Zhang L, et al. GLIPR-2 overexpression in HK-2 cells promotes cell EMT and migration through ERK1/2 activation. PLoS ONE. 2013;8:e58574 pubmed publisher
    ..GLIPR-2 may be responsible for the development of renal fibrosis by increasing the accumulation of interstitial fibroblasts. ..
  6. Gogl G, Töro I, Remenyi A. Protein-peptide complex crystallization: a case study on the ERK2 mitogen-activated protein kinase. Acta Crystallogr D Biol Crystallogr. 2013;69:486-9 pubmed publisher
    ..Furthermore, for extracellular signal-regulated kinase 2 (ERK2) the protein-peptide docking surface is comprised of a small hydrophobic surface patch that is often engaged in the ..
  7. Mace P, Wallez Y, Egger M, Dobaczewska M, Robinson H, Pasquale E, et al. Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK. Nat Commun. 2013;4:1681 pubmed publisher
    ..understand this ERK1/2 signalling complex, we have solved the crystal structures of PEA-15 bound to three different ERK2 phospho-conformers...
  8. Bouazza B, Debba Pavard M, Amrani Y, Isaacs L, O Connell D, Ahamed S, et al. Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid receptor function in airway smooth muscle cells. Am J Respir Cell Mol Biol. 2014;50:301-15 pubmed publisher
    ..Because p38 mitogen-activated protein kinase (MAPK) directly phosphorylates GR in different cell types in a stimulus- and cell-..
  9. Brown J, Kohler J, Coberley C, Sleasman J, Goodenow M. HIV-1 activates macrophages independent of Toll-like receptors. PLoS ONE. 2008;3:e3664 pubmed publisher
    ..HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches. ..
  10. Fiala M, Popik W, Qiao J, Lossinsky A, Alce T, Tran K, et al. HIV-1 induces cardiomyopathyby cardiomyocyte invasion and gp120, Tat, and cytokine apoptotic signaling. Cardiovasc Toxicol. 2004;4:97-107 pubmed
    ..HIV-1, gp120, or Tat induced Erk 1/2 phosphorylation, activation of caspase-3, and apoptosis of NRVMs and CAECs; all of these were inhibited by a ..

Detail Information

Publications92

  1. Smith E, Cai K, Smedberg J, Ribeiro M, Rula M, Slater C, et al. Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells. PLoS ONE. 2010;5:e9295 pubmed publisher
    ..Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription...
  2. Kuo H, Hsu H, Chang C, Jiang M, Yeh C, Shen K, et al. High nuclear phosphorylated extracellular signal-regulated kinase expression associated with poor differentiation, larger tumor size, and an advanced stage of breast cancer. Pol J Pathol. 2013;64:163-9 pubmed
    ..018) of the disease. Thus, nuclear phosphorylated ERK1/2 is associated with enhanced proliferation and invasion of mammary carcinomas and may be a biomarker for breast cancer prognosis and the determination of therapeutic strategies. ..
  3. Dyugovskaya L, Polyakov A, Cohen Kaplan V, Lavie P, Lavie L. Bax/Mcl-1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: effects of p38MAPK and ERK1/2 signaling. J Transl Med. 2012;10:211 pubmed publisher
    ..IH induced ERK1/2 and p38MAPKs phosphorylation, whereas SH induced only p38MAPK phosphorylation. Accordingly, both ERK and p38MAPK inhibitors attenuated the IH-induced Mcl-1 increase...
  4. Li Z, Li C, Du L, Zhou Y, Wu W. Human chorionic gonadotropin ? induces migration and invasion via activating ERK1/2 and MMP-2 in human prostate cancer DU145 cells. PLoS ONE. 2013;8:e54592 pubmed publisher
    ..These results indicated that hCG? induced cell motility via promoting ERK1/2 phosphorylation and MMP-2 upregulation in human prostate cancer DU145 cells. ..
  5. Huang S, Liu F, Niu Q, Li Y, Liu C, Zhang L, et al. GLIPR-2 overexpression in HK-2 cells promotes cell EMT and migration through ERK1/2 activation. PLoS ONE. 2013;8:e58574 pubmed publisher
    ..GLIPR-2 may be responsible for the development of renal fibrosis by increasing the accumulation of interstitial fibroblasts. ..
  6. Gogl G, Töro I, Remenyi A. Protein-peptide complex crystallization: a case study on the ERK2 mitogen-activated protein kinase. Acta Crystallogr D Biol Crystallogr. 2013;69:486-9 pubmed publisher
    ..Furthermore, for extracellular signal-regulated kinase 2 (ERK2) the protein-peptide docking surface is comprised of a small hydrophobic surface patch that is often engaged in the ..
  7. Mace P, Wallez Y, Egger M, Dobaczewska M, Robinson H, Pasquale E, et al. Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK. Nat Commun. 2013;4:1681 pubmed publisher
    ..understand this ERK1/2 signalling complex, we have solved the crystal structures of PEA-15 bound to three different ERK2 phospho-conformers...
  8. Bouazza B, Debba Pavard M, Amrani Y, Isaacs L, O Connell D, Ahamed S, et al. Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid receptor function in airway smooth muscle cells. Am J Respir Cell Mol Biol. 2014;50:301-15 pubmed publisher
    ..Because p38 mitogen-activated protein kinase (MAPK) directly phosphorylates GR in different cell types in a stimulus- and cell-..
  9. Brown J, Kohler J, Coberley C, Sleasman J, Goodenow M. HIV-1 activates macrophages independent of Toll-like receptors. PLoS ONE. 2008;3:e3664 pubmed publisher
    ..HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches. ..
  10. Fiala M, Popik W, Qiao J, Lossinsky A, Alce T, Tran K, et al. HIV-1 induces cardiomyopathyby cardiomyocyte invasion and gp120, Tat, and cytokine apoptotic signaling. Cardiovasc Toxicol. 2004;4:97-107 pubmed
    ..HIV-1, gp120, or Tat induced Erk 1/2 phosphorylation, activation of caspase-3, and apoptosis of NRVMs and CAECs; all of these were inhibited by a ..
  11. Tárrega C, Rios P, Cejudo Marín R, Blanco Aparicio C, van den Berk L, Schepens J, et al. ERK2 shows a restrictive and locally selective mechanism of recognition by its tyrosine phosphatase inactivators not shared by its activator MEK1. J Biol Chem. 2005;280:37885-94 pubmed
    The two regulatory residues that control the enzymatic activity of the mitogen-activated protein (MAP) kinase ERK2 are phosphorylated by the unique MAP kinase kinases MEK1/2 and dephosphorylated by several tyrosine-specific and dual ..
  12. Dickinson R, Williams D, Slack D, Williamson J, Seternes O, Keyse S. Characterization of a murine gene encoding a developmentally regulated cytoplasmic dual-specificity mitogen-activated protein kinase phosphatase. Biochem J. 2002;364:145-55 pubmed
    ..Our results suggest that this enzyme may have a critical role in regulating the activity of MAPK signalling during early development and organogenesis. ..
  13. Vomastek T, Iwanicki M, Burack W, Tiwari D, Kumar D, Parsons J, et al. 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;28:6954-66 pubmed publisher
    ..In previous work, we identified several new candidate substrates for the MAPK ERK2 (extracellular signal-regulated kinase 2), including the nuclear pore complex protein Tpr (translocated promoter ..
  14. Caunt C, McArdle C. Stimulus-induced uncoupling of extracellular signal-regulated kinase phosphorylation from nuclear localization is dependent on docking domain interactions. J Cell Sci. 2010;123:4310-20 pubmed publisher
    ..It was also evident with a catalytically inactive ERK2-GFP mutant, and with a mutant incapable of binding the DEF (docking site for ERK, F/Y-X-F/Y-P) domains found in ..
  15. Rowan B, Weigel N, O Malley B. Phosphorylation of steroid receptor coactivator-1. Identification of the phosphorylation sites and phosphorylation through the mitogen-activated protein kinase pathway. J Biol Chem. 2000;275:4475-83 pubmed
    ..395 and threonine 1179) contained a perfect consensus sequence for the mitogen-activated protein kinase family (Erk-1 and Erk-2)...
  16. Oh Hora M, Ogata M, Mori Y, Adachi M, Imai K, Kosugi A, et al. Direct suppression of TCR-mediated activation of extracellular signal-regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine-specific phosphatase. J Immunol. 1999;163:1282-8 pubmed
    ..LC-PTP dephosphorylated ERK2 in vitro...
  17. Chu Y, Solski P, Khosravi Far R, Der C, Kelly K. The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation. J Biol Chem. 1996;271:6497-501 pubmed
    ..A hyperactive allele of ERK2 (D319N), analogous to the Drosophila sevenmaker gain-of-function mutation, has significantly reduced sensitivity to ..
  18. Adams D, Coffee R, Zhang H, Pelech S, Strack S, Wadzinski B. Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by protein serine/threonine phosphatase 2A holoenzymes. J Biol Chem. 2005;280:42644-54 pubmed
    ..Pharmacological inhibitor studies as well as reporter assays for ERK-dependent activation of the transcription factor Elk1 revealed that the PP2A holoenzymes ABalphaC and ABdeltaC act ..
  19. Bai Y, Liu Y, Chen J, Song T, You Y, Tang Z, et al. Rosiglitazone attenuates NF-kappaB-dependent ICAM-1 and TNF-alpha production caused by homocysteine via inhibiting ERK1/2/p38MAPK activation. Biochem Biophys Res Commun. 2007;360:20-6 pubmed
    ..investigated the effects of Hcy on NF-kappaB-mediated sICAM-1, TNF-alpha production and the possible involvement of ERK(1/2)/p38MAPK pathway. The effects of rosiglitazone intervention were also examined...
  20. Hong F, Saiman Y, Si C, Mosoian A, Bansal M. X4 Human immunodeficiency virus type 1 gp120 promotes human hepatic stellate cell activation and collagen I expression through interactions with CXCR4. PLoS ONE. 2012;7:e33659 pubmed publisher
    ..Furthermore, X4 gp120 promoted Extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and pretreatment with an ERK inhibitor attenuated HSC activation and collagen I expression...
  21. Wang W, Chen J, Liao R, Deng Q, Zhou J, Huang S, et al. Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6-p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced premature senescence. Mol Cell Biol. 2002;22:3389-403 pubmed
    ..oncogenic ras induces premature senescence, depending on an active MEK-extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway...
  22. Whetzel A, Bolick D, Hedrick C. Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in endothelium through induction of MAP kinase phosphatase-3. Am J Physiol Cell Physiol. 2009;296:C339-45 pubmed publisher
    ..Thus, one mechanism for the anti-inflammatory action of S1P in diabetic EC is inhibition of ERK1/2 phosphorylation through induction of MKP-3 expression via the S1P-S1P(1) receptor axis. ..
  23. Kumar S, Jiang M, Adams J, Lee J. Pyridinylimidazole compound SB 203580 inhibits the activity but not the activation of p38 mitogen-activated protein kinase. Biochem Biophys Res Commun. 1999;263:825-31 pubmed
    b>p38 MAPK is a Ser/Thr protein kinase activated by various inflammatory cytokines and a variety of stress stimuli. It is involved in many physiological processes, including the production of inflammatory cytokines...
  24. Imasato A, Desbois Mouthon C, Han J, Kai H, Cato A, Akira S, et al. Inhibition of p38 MAPK by glucocorticoids via induction of MAPK phosphatase-1 enhances nontypeable Haemophilus influenzae-induced expression of toll-like receptor 2. J Biol Chem. 2002;277:47444-50 pubmed
    ..up-regulation of the MAPK phosphatase-1 (MKP-1) that, in turn, leads to dephosphorylation and inactivation of p38 MAPK, the negative regulator for TLR2 expression...
  25. 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;277:20631-9 pubmed
    ..These results highlight Sp1 as a key molecular link between elevated activation of the Ras > p42/p44MAPK signaling pathway and increased VEGF expression, two major steps deregulated in tumor cells. ..
  26. Dalby K, Morrice N, Caudwell F, Avruch J, Cohen P. Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK. J Biol Chem. 1998;273:1496-505 pubmed
    ..Ser222, Ser364, and Ser381 are situated in analogous positions to phosphorylation sites in protein kinase B, protein kinase C, and p70S6K, suggesting a common mechanism of activation for these growth factor-stimulated protein kinases. ..
  27. 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;21:5151-63 pubmed
    ..IEX-1 was isolated by phosphorylation screening with active ERK2 and found subsequently phosphorylated in vivo upon ERK activation...
  28. Chen R, Abate C, Blenis J. Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase. Proc Natl Acad Sci U S A. 1993;90:10952-6 pubmed
    ..This study suggests a role for nuclear RSK and MAP kinase in modulating newly synthesized c-Fos phosphorylation and downstream signaling. ..
  29. Wen Sheng W. ERK signaling pathway is involved in p15INK4b/p16INK4a expression and HepG2 growth inhibition triggered by TPA and Saikosaponin a. Oncogene. 2003;22:955-63 pubmed
    ..Western blot of three activated forms of mitogen-activated protein kinase (MAPK) (p-ERK, p-JNK and p-p38) demonstrated that phosphorylation of ERK is dramatically induced (11...
  30. Armstrong S, Caunt C, McArdle C. Gonadotropin-releasing hormone and protein kinase C signaling to ERK: spatiotemporal regulation of ERK by docking domains and dual-specificity phosphatases. Mol Endocrinol. 2009;23:510-9 pubmed publisher
    ..roles using short inhibitory RNA to knock down endogenous ERK, adenoviruses to express GnRH receptors and add-back ERK2-GFP, and automated microscopy to monitor ERK location and activation...
  31. Boulton T, Nye S, Robbins D, Ip N, Radziejewska E, Morgenbesser S, et al. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell. 1991;65:663-75 pubmed
    ..We now describe cloning and characterization of two ERK1-related kinases, ERK2 and ERK3, and provide evidence suggesting that there are additional ERK family members...
  32. Yan Y, Black C, Cao P, Haferbier J, Kolb R, Spieker R, et al. Gamma-irradiation-induced DNA damage checkpoint activation involves feedback regulation between extracellular signal-regulated kinase 1/2 and BRCA1. Cancer Res. 2008;68:5113-21 pubmed publisher
    ..These results implicate an important interaction between BRCA1 and ERK1/2 in the regulation of cellular response after IR-induced DNA damage in MCF-7 cells. ..
  33. Powell C, Wright M, Jackson R. p38mapk and MEK1/2 inhibition contribute to cellular oxidant injury after hypoxia. Am J Physiol Lung Cell Mol Physiol. 2004;286:L826-33 pubmed
    ..Stress-related signaling pathways in epithelial cells are modulated by hypoxia and confer protection from reoxygenation, since hypoxia and chemical inhibition of p38mapk and MEK1/2 similarly increase cytolysis resulting from O2-. ..
  34. 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;20:466-79 pubmed
    ..Here we have identified a novel site on p38 and ERK2 MAPKs that regulates the docking specificity towards MAPKAPKs...
  35. Zhang D, Guo M, Zhang W, Lu X. Adiponectin stimulates proliferation of adult hippocampal neural stem/progenitor cells through activation of p38 mitogen-activated protein kinase (p38MAPK)/glycogen synthase kinase 3? (GSK-3?)/?-catenin signaling cascade. J Biol Chem. 2011;286:44913-20 pubmed publisher
    ..Adiponectin activates AMP-activated protein kinase and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways in adult hNSCs...
  36. Conner S, Scott G, Aplin A. Adhesion-dependent activation of the ERK1/2 cascade is by-passed in melanoma cells. J Biol Chem. 2003;278:34548-54 pubmed
    ..These results indicate that alterations in the adhesion requirement for ERK1/2 signaling in melanocytes are associated with the acquisition of malignant cell behavior. ..
  37. Blanco Aparicio C, Torres J, Pulido R. A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase. J Cell Biol. 1999;147:1129-36 pubmed
    ..PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant...
  38. Chen J, Plotkin L, Aguirre J, Han L, Jilka R, Kousteni S, et al. Transient versus sustained phosphorylation and nuclear accumulation of ERKs underlie anti-versus pro-apoptotic effects of estrogens. J Biol Chem. 2005;280:4632-8 pubmed
    ..of leptomycin B-induced inhibition of ERK export from the nucleus or overexpression of a green fluorescent protein-ERK2 mutant that resides permanently in the nucleus, converted the anti-apoptotic effect of 17beta-estradiol to a pro-..
  39. Prast J, Saleh L, Husslein H, Sonderegger S, Helmer H, Knöfler M. Human chorionic gonadotropin stimulates trophoblast invasion through extracellularly regulated kinase and AKT signaling. Endocrinology. 2008;149:979-87 pubmed
    ..Addition of the hormone activated ERK-1/2 and AKT in SGHPL-5 cells and pure, extravillous trophoblasts...
  40. Sun H, Charles C, Lau L, Tonks N. MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell. 1993;75:487-93 pubmed
    ..factor-inducible gene, 3CH134, encodes a dual specificity phosphatase that dephosphorylates and inactivates p42MAPK both in vitro and in vivo. In vitro, 3CH134 protein dephosphorylates both T183 and Y185 in p42MAPK...
  41. Camps M, Nichols A, Gillieron C, Antonsson B, Muda M, Chabert C, et al. Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase. Science. 1998;280:1262-5 pubmed
    ..MKP-3 was activated by direct binding to purified ERK2. Activation was independent of protein kinase activity and required binding of ERK2 to the noncatalytic amino-..
  42. Bardwell A, Flatauer L, Matsukuma K, Thorner J, Bardwell L. A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and cooperates with a scaffold protein to enhance signal transmission. J Biol Chem. 2001;276:10374-86 pubmed
    ..sequences in human MEK1 and MEK2 are necessary and sufficient for the direct binding of the MAPKs ERK1 and ERK2. Mutations in MEK1, MEK2, or Ste7 that altered conserved residues in the docking site diminished binding of the ..
  43. Shi H, Asher C, Chigaev A, Yung Y, Reuveny E, Seger R, et al. Interactions of beta and gamma ENaC with Nedd4 can be facilitated by an ERK-mediated phosphorylation. J Biol Chem. 2002;277:13539-47 pubmed
    ..demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK)...
  44. Zhou B, Wang Z, Zhao Y, Brautigan D, Zhang Z. The specificity of extracellular signal-regulated kinase 2 dephosphorylation by protein phosphatases. J Biol Chem. 2002;277:31818-25 pubmed
    The extracellular signal-regulated protein kinase 2 (ERK2) is the founding member of a family of mitogen-activated protein kinases (MAPKs) that are central components of signal transduction pathways for cell proliferation, stress ..
  45. Roy M, Li Z, Sacks D. IQGAP1 binds ERK2 and modulates its activity. J Biol Chem. 2004;279:17329-37 pubmed
    ..In vitro analysis with purified proteins demonstrated a direct interaction between ERK2 and IQGAP1...
  46. Pulido R, Zuniga A, Ullrich A. PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ERK2 by association through a kinase interaction motif. EMBO J. 1998;17:7337-50 pubmed
    ..Co-expression of ERK2 with catalytically active PTP-SL in COS-7 cells impaired the EGF-induced activation of ERK2, whereas a PTP-SL ..
  47. Zuniga A, Torres J, Ubeda J, Pulido R. Interaction of mitogen-activated protein kinases with the kinase interaction motif of the tyrosine phosphatase PTP-SL provides substrate specificity and retains ERK2 in the cytoplasm. J Biol Chem. 1999;274:21900-7 pubmed
    ERK1 and ERK2 associate with the tyrosine phosphatase PTP-SL through a kinase interaction motif (KIM) located in the juxtamembrane region of PTP-SL...
  48. Bermudez O, Jouandin P, Rottier J, Bourcier C, Pages G, Gimond C. Post-transcriptional regulation of the DUSP6/MKP-3 phosphatase by MEK/ERK signaling and hypoxia. J Cell Physiol. 2011;226:276-84 pubmed publisher
    ..We first confirm the key role of MEK/ERK in maintaining the levels of dusp6 mRNA, while PI3K/mTOR, p38 MAPK, and JNK signaling pathways had no significant effects...
  49. Luttrell L, Roudabush F, Choy E, Miller W, Field M, Pierce K, et al. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc Natl Acad Sci U S A. 2001;98:2449-54 pubmed
    ..examined the role of beta-arrestins in the activation and targeting of extracellular signal-regulated kinase 2 (ERK2) following stimulation of angiotensin II type 1a receptors (AT1aR)...
  50. Tresini M, Lorenzini A, Frisoni L, Allen R, Cristofalo V. Lack of Elk-1 phosphorylation and dysregulation of the extracellular regulated kinase signaling pathway in senescent human fibroblast. Exp Cell Res. 2001;269:287-300 pubmed
    ..phosphorylation of p62(TCF)/Elk-1, which is catalyzed by the members of the extracellular-regulated kinase (ERK) family was strikingly diminished and correlated with a decrease in the abundance of activated ERK proteins...
  51. Yang H, Cohen P, Rousseau S. IL-1beta-stimulated activation of ERK1/2 and p38alpha MAPK mediates the transcriptional up-regulation of IL-6, IL-8 and GRO-alpha in HeLa cells. Cell Signal. 2008;20:375-80 pubmed
    ..Specific inhibition of p38alpha MAP kinase or preventing the activation of ERK1/ERK2 partially reduced the production of these substances, while the combined blockade of both pathways almost abolished ..
  52. Tsai E, Chan T, Chen Y, Hsu S, Chuang C, Lee J. Mifepristone attenuates human chorionic gonadotropin-induced extracellular signal-regulated kinase 1/2 phosphorylation, cyclooxygenase-2, and prostaglandin E2 production in human granulosa luteal cells. Fertil Steril. 2008;89:1522-9 pubmed
    ..To elucidate the role of RU486 in regulating the function of granulosa luteal cells and its possible involvement in ovarian dysfunction...
  53. Tomkowicz B, Lee C, Ravyn V, Cheung R, Ptasznik A, Collman R. The Src kinase Lyn is required for CCR5 signaling in response to MIP-1beta and R5 HIV-1 gp120 in human macrophages. Blood. 2006;108:1145-50 pubmed
    ..activation of Lyn and the concomitant Lyn-dependent activation of the mitogen-activated protein (MAP) kinase ERK-1/2...
  54. 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;22:8823-34 pubmed
    ..By site-directed mutagenesis studies, we demonstrate that the shift is due to an ERK2-mediated feedback phosphorylation of serine/threonine residues within an evolutionary conserved SPKTP motif at the ..
  55. 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;70:6701-8 pubmed
  56. Nishihara H, Hwang M, Kizaka Kondoh S, Eckmann L, Insel P. Cyclic AMP promotes cAMP-responsive element-binding protein-dependent induction of cellular inhibitor of apoptosis protein-2 and suppresses apoptosis of colon cancer cells through ERK1/2 and p38 MAPK. J Biol Chem. 2004;279:26176-83 pubmed
    ..pharmacological inhibitors revealed that cAMP-dependent phosphorylation of CREB required activation of ERK1/2 and p38 MAPK but was largely independent of protein kinase A...
  57. Silvers A, Bachelor M, Bowden G. The role of JNK and p38 MAPK activities in UVA-induced signaling pathways leading to AP-1 activation and c-Fos expression. Neoplasia. 2003;5:319-29 pubmed publisher
    ..UVA-induced phosphorylation of p38 and c-Jun N-terminal kinase (JNK) proteins was detected immediately after irradiation and disappeared after ..
  58. Whitehurst A, Cobb M, White M. Stimulus-coupled spatial restriction of extracellular signal-regulated kinase 1/2 activity contributes to the specificity of signal-response pathways. Mol Cell Biol. 2004;24:10145-50 pubmed
    ..One such module is the Raf-MEK-extracellular signal-regulated kinase (ERK) kinase cascade...
  59. Robinson F, Whitehurst A, Raman M, Cobb M. Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1. J Biol Chem. 2002;277:14844-52 pubmed
    Extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2) are essential components of pathways through which signals received at membrane receptors are converted into specific changes in protein function and gene expression...
  60. Hashiramoto A, Murata M, Kawazoe T, Yoshida K, Akiyama C, Shiozawa K, et al. Heat shock protein 90 maintains the tumour-like character of rheumatoid synovial cells by stabilizing integrin-linked kinase, extracellular signal-regulated kinase and protein kinase B. Rheumatology (Oxford). 2011;50:852-61 pubmed publisher
    ..The contribution of HSP90 is important in the pathogenesis of RA that potentiates a tumour-like synovial overgrowth by stabilizing ILK, extracellular signal-regulated kinase and Akt. ..
  61. Kinet S, Bernard F, Mongellaz C, Perreau M, Goldman F, Taylor N. gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4(+) lymphocytes. Blood. 2002;100:2546-53 pubmed
    ..These studies reveal a mechanism via which gp120 may differentially modulate the fate of activated and quiescent T cells in vivo. ..
  62. Handra Luca A, Bilal H, Bertrand J, Fouret P. Extra-cellular signal-regulated ERK-1/ERK-2 pathway activation in human salivary gland mucoepidermoid carcinoma: association to aggressive tumor behavior and tumor cell proliferation. Am J Pathol. 2003;163:957-67 pubmed
    ..Activation of extracellular signal-regulated kinases ERK-1 and ERK-2 is strongly correlated to cancer...
  63. Caunt C, Rivers C, Conway Campbell B, Norman M, McArdle C. Epidermal growth factor receptor and protein kinase C signaling to ERK2: spatiotemporal regulation of ERK2 by dual specificity phosphatases. J Biol Chem. 2008;283:6241-52 pubmed publisher
    ..microscopy in combination with a system where endogenous ERKs are removed and replaced with wild-type or mutated ERK2-green fluorescent protein (GFP), we show that ERK2 activation responses to epidermal growth factor (EGF) and ..
  64. Chuderland D, Konson A, Seger R. Identification and characterization of a general nuclear translocation signal in signaling proteins. Mol Cell. 2008;31:850-61 pubmed publisher
    ..identified a 3 amino acid domain (SPS) that is phosphorylated upon stimulation to induce nuclear translocation of ERK2. A 19 amino acid stretch containing this phosphorylated domain inserts nondiffusible proteins to the nucleus ..
  65. Jinawath A, Akiyama Y, Yuasa Y, Pairojkul C. Expression of phosphorylated ERK1/2 and homeodomain protein CDX2 in cholangiocarcinoma. J Cancer Res Clin Oncol. 2006;132:805-10 pubmed
    The extracellular signal-regulated kinase (ERK) 1/2 pathway plays important roles in the regulation of cell proliferation, differentiation and cell survival...
  66. Formstecher E, Ramos J, Fauquet M, Calderwood D, Hsieh J, Canton B, et al. PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase. Dev Cell. 2001;1:239-50 pubmed
    The ERK 1/2 MAP kinase pathway controls cell growth and survival and modulates integrin function...
  67. Eblen S, Kumar N, Shah K, Henderson M, Watts C, Shokat K, et al. Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs. J Biol Chem. 2003;278:14926-35 pubmed
    ..As a first step in achieving this goal, we engineered a mutant ERK2 in which a bulky amino acid residue in the ATP binding site (glutamine 103) is changed to glycine, allowing this ..
  68. Toschi E, Bacigalupo I, Strippoli R, Chiozzini C, Cereseto A, Falchi M, et al. HIV-1 Tat regulates endothelial cell cycle progression via activation of the Ras/ERK MAPK signaling pathway. Mol Biol Cell. 2006;17:1985-94 pubmed
    ..cells results in the activation of the small GTPases Ras and Rac and the mitogen-activated protein kinase ERK, specifically through its RGD region...
  69. Schmitz K, Wohlschlaeger J, Alakus H, Bohr J, Stauder M, Worm K, et al. Activation of extracellular regulated kinases (ERK1/2) but not AKT predicts poor prognosis in colorectal carcinoma and is associated with k-ras mutations. Virchows Arch. 2007;450:151-9 pubmed
    ..We propose immunohistochemical determination of pERK1/2 status as a promising candidate for the identification of high-risk patients who would benefit from new anticancer drugs targeting the ERK pathway.
  70. Hayashi K, Pu H, Andras I, Eum S, Yamauchi A, Hennig B, et al. HIV-TAT protein upregulates expression of multidrug resistance protein 1 in the blood-brain barrier. J Cereb Blood Flow Metab. 2006;26:1052-65 pubmed
    ..These results indicate that Tat exposure can lead to alterations of the BBB functions and decrease HAART efficacy in the CNS through overexpression of drug efflux transporters. ..
  71. Mizumoto Y, Kyo S, Mori N, Sakaguchi J, Ohno S, Maida Y, et al. Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis. Cancer Sci. 2007;98:652-8 pubmed
    The extracellular-regulated kinase (ERK) signaling pathway plays important roles in regulating the malignant potential of cancer cells in vitro...
  72. Bukrinskaya A, Ghorpade A, Heinzinger N, Smithgall T, Lewis R, Stevenson M. Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA. Proc Natl Acad Sci U S A. 1996;93:367-71 pubmed
    ..These results reveal a novel level of regulation of primate lentivirus infectivity. ..
  73. Jacque J, Mann A, Enslen H, Sharova N, Brichacek B, Davis R, et al. Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase. EMBO J. 1998;17:2607-18 pubmed
    ..In this study, we identify the virion-associated kinase as mitogen-activated protein kinase (ERK/MAPK)...
  74. Mangino G, Percario Z, Fiorucci G, Vaccari G, Manrique S, Romeo G, et al. In vitro treatment of human monocytes/macrophages with myristoylated recombinant Nef of human immunodeficiency virus type 1 leads to the activation of mitogen-activated protein kinases, IkappaB kinases, and interferon regulatory factor 3 and to the r. J Virol. 2007;81:2777-91 pubmed
    ..and transient phosphorylation of the alpha and beta subunits of the IkappaB kinase complex and of JNK, ERK1/2, and p38 mitogen-activated protein kinase family members...
  75. Bai L, Zhang Z, Zhang H, Li X, Yu Q, Lin H, et al. HIV-1 Tat protein alter the tight junction integrity and function of retinal pigment epithelium: an in vitro study. BMC Infect Dis. 2008;8:77 pubmed publisher
    ..The effects of HIV-1 Tat on barrier function of the RPE may be mediated by ERK MAPK and NF-kappaB activation, which may represent potential targets for novel therapeutic approaches for the ..
  76. Patel D, King C, Bailey S, Holt J, Venkatachalam K, Agrawal A, et al. Interleukin-17 stimulates C-reactive protein expression in hepatocytes and smooth muscle cells via p38 MAPK and ERK1/2-dependent NF-kappaB and C/EBPbeta activation. J Biol Chem. 2007;282:27229-38 pubmed
    ..Overexpression of wild type p50, p65, and C/EBPbeta stimulated CRP transcription. IL-17 stimulated p38 MAPK and ERK1/2 activation, and SB203580 and PD98059 blunted IL-17-mediated NF-kappaB and C/EBP activation and CRP ..
  77. Mishra M, Taneja M, Malik S, Khalique H, Seth P. Human immunodeficiency virus type 1 Tat modulates proliferation and differentiation of human neural precursor cells: implication in NeuroAIDS. J Neurovirol. 2010;16:355-67 pubmed publisher
    ..Validation with autopsy brain samples is necessary to further substantiate these important observations. ..
  78. Yang C, Luo S, Hsieh H, Chi P, Lin C, Wu C, et al. Interleukin-1beta induces ICAM-1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts: involvement of ERK, JNK, AP-1, and NF-kappaB. J Cell Physiol. 2010;224:516-26 pubmed publisher
    ..IL-1beta-induced ICAM-1 expression, extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 ..
  79. Pandey P, Udayakumar T, Lin X, Sharma D, Shapiro P, Fondell J. Activation of TRAP/mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation. Mol Cell Biol. 2005;25:10695-710 pubmed
    ..We show here that human TRAP220/Med1 is a specific substrate for extracellular signal-regulated kinase (ERK) of the mitogen-activated protein kinase (MAPK) family...
  80. Mandl M, Slack D, Keyse S. Specific inactivation and nuclear anchoring of extracellular signal-regulated kinase 2 by the inducible dual-specificity protein phosphatase DUSP5. Mol Cell Biol. 2005;25:1830-45 pubmed
    ..which determine the nuclear accumulation and inactivation of the extracellular signal-regulated kinase 1 (ERK1) or ERK2 mitogen-activated protein (MAP) kinases are poorly understood...
  81. Badou A, Bennasser Y, Moreau M, Leclerc C, Benkirane M, Bahraoui E. Tat protein of human immunodeficiency virus type 1 induces interleukin-10 in human peripheral blood monocytes: implication of protein kinase C-dependent pathway. J Virol. 2000;74:10551-62 pubmed
    ..factor NF-kappaB and in the induction of phosphorylation of the mitogen-activated protein kinases ERK1 and ERK2; activation of these two potential substrates of protein kinase C is required for the production of IL-10...
  82. Chihara T, Hashimoto M, Osman A, Hiyoshi Yoshidomi Y, Suzu I, Chutiwitoonchai N, et al. HIV-1 proteins preferentially activate anti-inflammatory M2-type macrophages. J Immunol. 2012;188:3620-7 pubmed publisher
  83. Saxena M, Williams S, Brockdorff J, Gilman J, Mustelin T. Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP). J Biol Chem. 1999;274:11693-700 pubmed
    ..The specificity of HePTP correlated with its physical association through its noncatalytic N terminus with Erk and another MAP kinase, p38, but not Jnk or other proteins...
  84. Roux P, Ballif B, Anjum R, Gygi S, Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci U S A. 2004;101:13489-94 pubmed
    ..Together, our data unveil a regulatory mechanism by which the Ras/MAPK and PI3K pathways converge on the tumor suppressor tuberin to inhibit its function. ..
  85. Dowd S, Sneddon A, Keyse S. Isolation of the human genes encoding the pyst1 and Pyst2 phosphatases: characterisation of Pyst2 as a cytosolic dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases. J Cell Sci. 1998;111 ( Pt 22):3389-99 pubmed
    ..In common with Pyst1, Pyst2 shows substrate selectivity for the classical p42 (ERK2) isoform of MAP kinase both in vitro and in vivo, displaying much reduced activity towards stress activated MAP ..
  86. Hu S, Xie Z, Onishi A, Yu X, Jiang L, Lin J, et al. Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell. 2009;139:610-22 pubmed publisher
    ..One such uDBP, ERK2, acts as a transcriptional repressor for interferon gamma-induced genes, suggesting important biological roles for ..
  87. Dimitri C, Dowdle W, Mackeigan J, Blenis J, Murphy L. Spatially separate docking sites on ERK2 regulate distinct signaling events in vivo. Curr Biol. 2005;15:1319-24 pubmed
    ..We have examined the in vivo activity of ERK2 mutants with impaired ability to signal via either docking site...
  88. Song H, Ju S, Seo W, Goh A, Lee J, Bae Y, et al. Nox2-based NADPH oxidase mediates HIV-1 Tat-induced up-regulation of VCAM-1/ICAM-1 and subsequent monocyte adhesion in human astrocytes. Free Radic Biol Med. 2011;50:576-84 pubmed publisher
    ..siRNA decreased HIV-1 Tat-induced NF-?B activation as well as activation of MAP kinases including ERK, JNK, and p38. These data indicate that Nox2-based NADPH oxidase is responsible for HIV-1 Tat-induced generation of ROS and plays ..
  89. Casar B, Sanz Moreno V, Yazicioglu M, Rodriguez J, Berciano M, Lafarga M, et al. Mxi2 promotes stimulus-independent ERK nuclear translocation. EMBO J. 2007;26:635-46 pubmed
    ..This process requires the direct interaction of both proteins and a high-affinity binding of Mxi2 to ERK-binding sites in nucleoporins, In this respect, Mxi2 acts antagonistically to PEA15, displacing it from ERK1/2 ..
  90. Verma A, Mohindru M, Deb D, Sassano A, Kambhampati S, Ravandi F, et al. Activation of Rac1 and the p38 mitogen-activated protein kinase pathway in response to arsenic trioxide. J Biol Chem. 2002;277:44988-95 pubmed
    ..that arsenic trioxide induces activation of the small G-protein Rac1 and the alpha and beta isoforms of the p38 mitogen-activated protein (MAP) kinase in several leukemia cell lines...
  91. Vitale M, Matteucci A, Manzoli L, Rodella L, Mariani A, Zauli G, et al. Interleukin 2 activates nuclear phospholipase Cbeta by mitogen-activated protein kinase-dependent phosphorylation in human natural killer cells. FASEB J. 2001;15:1789-91 pubmed