Protein Information

Name ERK1
Synonyms ERK 1; ERK1; ERT 2; ERT2; Extracellular signal regulated kinase 1; Extracellular signal related kinase 1b; Extracellular signal related kinase 1c; HS44KDAP…

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
18474417 Zanotto-Filho A, Cammarota M, Gelain DP, Oliveira RB, Delgado-Canedo A, Dalmolin RJ, Pasquali MA, Moreira JC: Retinoic acid induces apoptosis by a non-classical mechanism of ERK1/2 activation. Toxicol In Vitro. 2008 Aug;22(5):1205-12. Epub 2008 Apr 7.

ERK1/2 activation was mediated by MEK1/2, and the protein synthesis inhibitor cycloheximide did not alter the pattern of RA-induced ERK1/2 phosphorylation.
2(0,0,0,2) Details
18417179 Asare N, Landvik NE, Lagadic-Gossmann D, Rissel M, Tekpli X, Ask K, Lag M, Holme JA: 1-Nitropyrene (1-NP) induces apoptosis and apparently a non-apoptotic programmed cell death (paraptosis) in Hepa1c1c7 cells. Toxicol Appl Pharmacol. 2008 Jul 15;230(2):175-86. Epub 2008 Feb 29.

In contrast, cycloheximide markedly reduced both the number of apoptotic and PI-positive cells as well as the cytoplasmic vacuolization, suggesting that 1-NP induced paraptotic cell death.
All the MAPKs; ERK1/2, p38 and JNK, appear to be involved in the death process since marked activation was observed upon 1-NP exposure, and their inhibitors partly reduced the induced cell death.
2(0,0,0,2) Details
19307750 Nakamura M, Ozaki T, Ishii A, Konishi M, Tsubota Y, Furui T, Tsuda H, Mori I, Ota K, Kakudo K: Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells. Exp Mol Med. 2009 May 31;41(5):307-15.

Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins.
2(0,0,0,2) Details
19041363 Asare N, Lag M, Lagadic-Gossmann D, Rissel M, Schwarze P, Holme JA: 3-Nitrofluoranthene (3-NF) but not 3-aminofluoranthene (3-AF) elicits apoptosis as well as programmed necrosis in Hepa1c1c7 cells. Toxicology. 2009 Jan 31;255(3):140-50. Epub 2008 Nov 7.

Cycloheximide completely attenuated 3-NF-induced cell death.
Increase in the number as well as size of lysosomes, myelinosomes, and activation of autophagy were also observed. 3-NF induced phosphorylation of ERK1/2, JNK and p38 MAPKs.
2(0,0,0,2) Details
19438724 Terasawa K, Ichimura A, Sato F, Shimizu K, Tsujimoto G: Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells. FEBS J. 2009 Jun;276(12):3269-76. Epub 2009 Apr 25.

2(0,0,0,2) Details
18223264 Molloy ES, Morgan MP, Doherty GA, McDonnell B, O'Byrne J, Fitzgerald DJ, McCarthy GM: Mechanism of basic calcium phosphate crystal-stimulated matrix metalloproteinase-13 expression by osteoarthritic synovial fibroblasts: inhibition by prostaglandin E2. Ann Rheum Dis. 2008 Dec;67(12):1773-9. Epub 2008 Jan 26.


BCP crystal-stimulated MMP-13 mRNA expression was blocked by inhibition of the extracellular regulated kinase (ERK1/2) and p38 mitogen activated protein kinase (MAPK) pathways and inhibition of the activation of nuclear factor kappaB.
2(0,0,0,2) Details
19716839 Charlson AT, Zeliadt NA, Wattenberg EV: Extracellular signal regulated kinase 5 mediates signals triggered by the novel tumor promoter palytoxin. Toxicol Appl Pharmacol. 2009 Dec 1;241(2):143-53. Epub 2009 Aug 28.

Cycloheximide, okadaic acid, and sodium orthovanadate did not mimic the effect of palytoxin on ERK5.
We previously showed that palytoxin activates three major members of the mitogen activated protein kinase (MAPK) family, extracellular signal regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38.
2(0,0,0,2) Details
18275597 Cullingford TE, Markou T, Fuller SJ, Giraldo A, Pikkarainen S, Zoumpoulidou G, Alsafi A, Ekere C, Kemp TJ, Dennis JL, Game L, Sugden PH, Clerk A: Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes. Genome Biol. 2008;9(2):R32. Epub 2008 Feb 14.

RESULTS: Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide.
Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited > 50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%.
2(0,0,0,2) Details
18336852 Lin CC, Tseng HW, Hsieh HL, Lee CW, Wu CY, Cheng CY, Yang CM: Tumor necrosis factor-alpha induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclear factor-kappaB in A549 cells. Toxicol Appl Pharmacol. 2008 Jun 15;229(3):386-98. Epub 2008 Feb 9.

Moreover, pretreatment with actinomycin D and cycloheximide attenuated TNF-alpha-induced MMP-9 expression.
2(0,0,0,2) Details
17182689 Mangino G, Percario ZA, Fiorucci G, Vaccari G, Manrique S, Romeo G, Federico M, Geyer M, Affabris E: 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 release of beta interferon. J Virol. 2007 Mar;81(6):2777-91. Epub 2006 Dec 20.

Previously, we reported that Nef treatment of primary human monocyte-derived macrophages (MDMs) induces a cycloheximide-independent activation of NF-kappaB and the synthesis and secretion of a set of chemokines/cytokines that activate STAT1 and STAT3.
Here, we show that Nef treatment is capable of hijacking cellular signaling pathways, inducing a very rapid regulatory response in MDMs that is characterized by the rapid 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.
1(0,0,0,1) Details
16602240 Karitskaia IA, Aksenov ND, Vinogradova TA, Marakhova II: [Il-2-regulated expression of Na+,K (+)-ATPase in activated human lymphocytes]. Tsitologiia. 2005;47(1):28-37.

A translation inhibitor cycloheximide was found to prevent the late increase in alfa1-subunit expression.
A decrease in alfa1-protein accumulation in the presence of specific inhibitors of separate signal transduction pathways enables us to conclude that protein kinases ERK1/2 (MAPK pathway) and JAK3 (JAK-STAT pathway) mediate the IL-2-dependent regulation of Na+,K (+)-ATPase expression during lymphocyte transition from resting stage to proliferation.
1(0,0,0,1) Details
17067562 Frias MA, Rebsamen MC, Gerber-Wicht C, Lang U: Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy. Cardiovasc Res. 2007 Jan 1;73(1):57-65. Epub 2006 Sep 27.

The activation of Stat3 occurs mainly through EP4 and involves ERK1/2 as well as newly synthesized protein (s).
Nuclear Stat3 phosphorylation induced by PGE2 is also suppressed by the translation and transcription inhibitors, cycloheximide and actinomycin D, respectively.
1(0,0,0,1) Details
17264307 Ratthe C, Pelletier M, Chiasson S, Girard D: Molecular mechanisms involved in interleukin-4-induced human neutrophils: expression and regulation of suppressor of cytokine signaling. J Leukoc Biol. 2007 May;81(5):1287-96. Epub 2007 Jan 30.

The effect of IL-4 on SOCS3 protein expression was increased markedly when the proteasome inhibitor MG132 was added to the cultures, but this was inhibited by cycloheximide, suggesting that SOCS3 is de novo-synthesized in response to IL-4.
We also demonstrated that IL-4 induced phosphorylation of Syk, p38, Erk-1/2, JNK, Jak-1, Jak-2, STAT6, and STAT1 and that treatment of cells with the inhibitors piceatannol, SB203580, PD98059, or AG490 reversed the ability of IL-4 to delay neutrophil apoptosis.
1(0,0,0,1) Details
16109713 Rahmani M, Davis EM, Bauer C, Dent P, Grant S: Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation. J Biol Chem. 2005 Oct 21;280(42):35217-27. Epub 2005 Aug 18.

These events were accompanied by ERK1/2 inactivation and caspase-independent down-regulation of Mcl-1.
Inhibition of protein synthesis by cycloheximide or proteasome function with MG132 and pulse-chase studies with [35S] methionine demonstrated that BAY 43-9006 did not diminish Mcl-1 protein stability, nor did it enhance Mcl-1 ubiquitination, but instead markedly attenuated Mcl-1 translation in association with the rapid and potent dephosphorylation of the eIF4E translation initiation factor.
1(0,0,0,1) Details
16669788 Bhattacharya S, Ray RM, Johnson LR: Integrin beta3-mediated Src activation regulates apoptosis in IEC-6 cells via Akt and STAT3. Biochem J. 2006 Aug 1;397(3):437-47.

Arg-Gly-Asp-Ser inhibited beta3, Src and Akt phosphorylation and sensitized polyamine-depleted cells to tumour necrosis factor alpha/cycloheximide-mediated apoptosis.
Inhibition of ODC by DFMO (alpha-difluoromethylornithine) increased the activity of Src and ERK1/2 (extracellular-signal-regulated kinase 1/2) within 30 min, which was prevented by exogenous polyamines added to the DFMO-containing medium.
1(0,0,0,1) Details
18339016 Fujisawa T, Ide K, Holtzman MJ, Suda T, Suzuki K, Kuroishi S, Chida K, Nakamura H: Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells. Respirology. 2008 Mar;13(2):191-202.

Cycloheximide also diminished activation of p38 MAPK and induction of MUC5AC mRNA expression by IL-13.
Western blotting was used to assess activation of the signalling molecules, signal transducer and activator of transcription 6 (STAT6), p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2.
1(0,0,0,1) Details
16644694 Koehler JA, Drucker DJ: Activation of glucagon-like peptide-1 receptor signaling does not modify the growth or apoptosis of human pancreatic cancer cells. Diabetes. 2006 May;55(5):1369-79.

Conversely, Ex-4 induced extracellular regulated kinase (ERK) 1/2 activation in PL 45 cells in a GLP-1R-and epidermal growth factor receptor-dependent manner, whereas Ex-4 inhibited ERK1/2 phosphorylation in Hs 766T and CAPAN-1 cells.
Ex-4 did not modulate the proliferation of these cell lines in vitro and did not inhibit apoptosis after exposure of cells to cytotoxic agents such as cycloheximide, indomethacin, LY294002, or cyclopamine.
1(0,0,0,1) Details
19289468 Kurada BR, Li LC, Mulherkar N, Subramanian M, Prasad KV, Prabhakar BS: MADD, a splice variant of IG20, is indispensable for MAPK activation and protection against apoptosis upon tumor necrosis factor-alpha treatment. J Biol Chem. 2009 May 15;284(20):13533-41. Epub 2009 Mar 16.

We investigated the physiological role of endogenous MAPK-activating death domain-containing protein (MADD), a splice variant of the IG20 gene, that can interact with TNFR1 in tumor necrosis factor-alpha (TNFalpha)-induced activation of NF-kappaB, MAPK, ERK1/2, JNK, and p38.
Abrogation of MADD expression rendered cells highly susceptible to TNFalpha-induced apoptosis in the absence of cycloheximide.
1(0,0,0,1) Details
15666812 Clark BJ, Li J: Janus kinase 2 signaling in the angiotensin II-dependent activation of StAR expression. Endocr Res. 2004 Nov;30(4):685-93.

Using StAR promoter-reporter gene activity and pharmacological inhibition of signaling pathways, we have shown that Ang II-stimulated StAR transcription in H295R cells is dependent upon both influx of external Ca2+ and tyrosine kinase signaling and is enhanced by protein kinase C and mitogen-activated protein kinase (ERK1/2) activation.
The Ang II-dependent, but not (Bu) 2cAMP-dependent, induction of StAR mRNA was also blocked by AG490 and shown to be sensitive to cycloheximide treatment.
1(0,0,0,1) Details
16684952 Cohen M, Marchand-Adam S, Lecon-Malas V, Marchal-Somme J, Boutten A, Durand G, Crestani B, Dehoux M: HGF synthesis in human lung fibroblasts is regulated by oncostatin M. . Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1097-103.

OSM-induced HGF secretion was inhibited by PD-98059 (a specific pharmacological inhibitor of ERK1/2), SB-203580 (a p38 MAPK inhibitor), and SP-600125 (a JNK inhibitor) by 70, 82, and 100%, respectively, whereas basal HGF secretion was only inhibited by SP-600125 by 30%.
HGF was released in its cleaved mature form, and its secretion was completely inhibited in the presence of cycloheximide, indicating a de novo protein synthesis.
1(0,0,0,1) Details
18347988 Doubravska L, Simova S, Cermak L, Valenta T, Korinek V, Andera L: Wnt-expressing rat embryonic fibroblasts suppress Apo2L/TRAIL-induced apoptosis of human leukemia cells. Apoptosis. 2008 Apr;13(4):573-87. Epub 2008 Mar 18.


This anti-apoptotic signaling was significantly hampered by the inhibition of the MEK1/ERK1/2 or NFkappaB pathways in KM3 and REH cells.
1(0,0,0,1) Details
16298406 Urbach V, Verriere V, Grumbach Y, Bousquet J, Harvey BJ: Rapid anti-secretory effects of glucocorticoids in human airway epithelium. Steroids. 2006 Apr;71(4):323-8. Epub 2005 Nov 18.

The rapid responses to glucocorticoid were reduced by the inhibitors of adenylated cyclase, cAMP-dependent protein kinase (PKA) and mitogen-activated protein kinase (ERK1/2).
The rapid effects of dexamethasone on intracellular pH and Ca (2+) were not affected by inhibitors of transcription, cycloheximide or by the classical glucocorticoid and mineralocorticoid receptors antagonists, RU486 and spironolactone, respectively.
1(0,0,0,1) Details
20339118 Montezano AC, Burger D, Paravicini TM, Chignalia AZ, Yusuf H, Almasri M, He Y, Callera GE, He G, Krause KH, Lambeth D, Quinn MT, Touyz RM: Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 5 (Nox5) Regulation by Angiotensin II and Endothelin-1 Is Mediated via Calcium/Calmodulin-Dependent, Rac-1-Independent Pathways in Human Endothelial Cells. Circ Res. 2010 Mar 25.

Nox5 activation by Ang II and ET-1 induces ROS generation and ERK1/2 phosphorylation.
Effects were inhibited by actinomycin D and cycloheximide and blunted by diltiazem, calmidazolium and low extracellular Ca (2+) ([Ca (2+)] e).
1(0,0,0,1) Details
15962305 Laury-Kleintop LD, Tresini M, Hammond O: Compartmentalization of hnRNP-K during cell cycle progression and its interaction with calponin in the cytoplasm. J Cell Biochem. 2005 Aug 1;95(5):1042-56.

Using cycloheximide, we observed that cytoplasmic accumulation of hnRNP-K protein at later time points in the cell cycle occurred with a concomitant decrease in nuclear hnRNP-K protein, suggesting a translocation of nuclear hnRNP-K protein to the cytoplasm.
When present in the cytoplasm, hnRNP-K is part of a multi-protein complex that consists of at least two other proteins, calponin and ERK1/2.
1(0,0,0,1) Details
19553664 Sommerfeld A, Reinehr R, Haussinger D: Bile acid-induced epidermal growth factor receptor activation in quiescent rat hepatic stellate cells can trigger both proliferation and apoptosis. J Biol Chem. 2009 Aug 14;284(33):22173-83. Epub 2009 Jun 24.


When, however, a JNK signal was induced by coadministration of cycloheximide or hydrogen peroxide (H2O2), activated EGFR associated with CD95 and triggered EGFR-mediated CD95-tyrosine phosphorylation and subsequent formation of the death-inducing signaling complex.
0(0,0,0,0) Details
16492674 Berry FB, Mirzayans F, Walter MA: Regulation of FOXC1 stability and transcriptional activity by an epidermal growth factor-activated mitogen-activated protein kinase signaling cascade. J Biol Chem. 2006 Apr 14;281(15):10098-104. Epub 2006 Feb 21.


Furthermore, we have demonstrated that activation of the ERK1/2 mitogen-activated protein kinase through epidermal growth factor stimulation is required for maximal FOXC1 transcriptional activation and stability.
1(0,0,0,1) Details
16714403 Martinez JM, Sali T, Okazaki R, Anna C, Hollingshead M, Hose C, Monks A, Walker NJ, Baek SJ, Eling TE: Drug-induced expression of nonsteroidal anti-inflammatory drug-activated gene/macrophage inhibitory cytokine-1/prostate-derived factor, a putative tumor suppressor, inhibits tumor growth. J Pharmacol Exp Ther. 2006 Aug;318(2):899-906. Epub 2006 May 19.


Extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was increased by 5F203, and inhibition of ERK1/2 phosphorylation abolished the induction of NAG-1 protein expression and increased the stability of NAG-1 mRNA.
1(0,0,0,1) Details
15805247 Cinar B, De Benedetti A, Freeman MR: Post-transcriptional regulation of the androgen receptor by Mammalian target of rapamycin. Cancer Res. 2005 Apr 1;65(7):2547-53.


The signal to attenuate AR was mediated by the mammalian target of rapamycin, as shown by genetic and pharmacologic methods, and was independent of ErbB2/HER-2, extracellular signal-regulated kinase 1/2, and p38 mitogen-activated protein kinase pathways.
1(0,0,0,1) Details
18410509 Messina S, Molinaro G, Bruno V, Battaglia G, Spinsanti P, Di Pardo A, Nicoletti F, Frati L, Porcellini A: Enhanced expression of Harvey ras induced by serum deprivation in cultured astrocytes. J Neurochem. 2008 Jul;106(2):551-9. Epub 2008 Apr 12.

Serum deprivation led to the activation of the MAPK pathway in cultured astrocytes, as shown by an increase in phosphorylated extracellular signal-regulated kinase 1/2 levels after 5 and 30 min.
The increase in Ha-Ras levels was sensitive to the protein synthesis inhibitor, cycloheximide, suggesting that serum deprivation increases translation of preformed Ha-Ras mRNA.
1(0,0,0,1) Details
19777442 Pucci B, Indelicato M, Paradisi V, Reali V, Pellegrini L, Aventaggiato M, Karpinich NO, Fini M, Russo MA, Farber JL, Tafani M: ERK-1 MAP kinase prevents TNF-induced apoptosis through bad phosphorylation and inhibition of Bax translocation in HeLa Cells. J Cell Biochem. 2009 Dec 1;108(5):1166-74.


Extracellular signal-regulated kinase (ERK) 1/2 signaling is involved in tumor cell survival through the regulation of Bcl-2 family members.
1(0,0,0,1) Details
20352599 Hahner S, Sturmer A, Fassnacht M, Hartmann RW, Schewe K, Cochran S, Zink M, Schirbel A, Allolio B: Etomidate Unmasks Intraadrenal Regulation of Steroidogenesis and Proliferation in Adrenal Cortical Cell Lines. Horm Metab Res. 2010 Mar 29.

The increase in protein levels was partially reversed by cycloheximide suggesting post-transcriptional mechanisms but also protein stabilization as underlying cause.
Furthermore, ETO exhibited antiproliferative activity paralleled by a decrease in phosphorylation of MEK and ERK1, 2.
1(0,0,0,1) Details
15633612 Yang S, Yip R, Polena S, Sharma M, Rao S, Griciene P, Gintautas J, Jerome H: Reactive oxygen species increased focal adhesion kinase production in pulmonary microvascular endothelial cells. Proc West Pharmacol Soc. 2004;47:54-6.

Activation of p44 and p42 extracellular signal-regulated protein kinases (ERK1 and ERK2) is an important step in the cascade leading to cell growth and proliferation.
We found that low dose H2O2 induced increased FAK production in pulmonary microvascular endothelial cells, which could be blocked by cycloheximide (CHX), a protein synthesis inhibitor.
1(0,0,0,1) Details
16467189 El Sayah M, Medeiros R, Fernandes ES, Campos MM, Calixto JB: Mechanisms underlying lipopolysaccharide-induced kinin B1 receptor up-regulation in the pig iris sphincter in vitro. Mol Pharmacol. 2006 May;69(5):1701-8. Epub 2006 Feb 7.

The up-regulation of B1 receptors by lipopolysaccharide stimulation was decreased by the inhibitors of protein synthesis, cycloheximide and actinomycin D, and by dexamethasone and the nuclear factor-kappaB (NF-kappaB) inhibitor pyrrolidinedithiocarbamate (PDTC).
In addition, lipopolysaccharide-induced up-regulation of B1 receptors in the pig iris sphincter was significantly reduced by the p38 inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl) 1H-imidazole (SB203580) and to a lesser extent by the extracellular signal-regulated kinases 1 and 2 (ERK1/2) blocker 2'-amino-3'-methoxyflavone (PD98059).
2(0,0,0,2) Details
16805793 Sugano T, Yanagita T, Yokoo H, Satoh S, Kobayashi H, Wada A: Enhancement of insulin-induced PI3K/Akt/GSK-3beta and ERK signaling by neuronal nicotinic receptor/PKC-alpha/ERK pathway: up-regulation of IRS-1/-2 mRNA and protein in adrenal chromaffin cells. J Neurochem. 2006 Jul;98(1):20-33.

In cultured bovine adrenal chromaffin cells treated with nicotine (10 microm for 24 h), phosphorylation of Akt, glycogen synthase kinase-3beta (GSK-3beta) and extracellular signal-regulated kinase (ERK) 1/2 induced by insulin (100 nm for 10 min) was enhanced by approximately 62%, without altering levels of these protein kinases.
The increase in IRS-1/IRS-2 levels induced by nicotine was prevented by nicotinic acetylcholine receptor (nAChR) antagonists, the Ca (2+) chelator 1,2-bis (2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid tetrakis-acetoxymethyl ester, cycloheximide or actinomycin D.
2(0,0,0,2) Details
16786197 Li Z, Zong H, Kong X, Zhang S, Wang H, Sun Q, Gu J: Cell surface beta 1, 4-galactosyltransferase 1 promotes apoptosis by inhibiting epidermal growth factor receptor pathway. Mol Cell Biochem. 2006 Oct;291(1-2):69-76. Epub 2006 Jun 20.

Our previous studies have shown that overexpression of beta1,4-galactosyltransferase1 (beta1,4GT1) leads to increased apoptosis induced by cycloheximide (CHX) in SMMC-7721 human hepatocarcinoma cells.
The phosphorylation of protein kinase B (PKB/Akt) and extracellular signal-regulated protein kinase1/2 (ERK1/2), which are downstream molecules of EGFR, were also reduced in cell surface beta1,4GT1-overexpressing cells.
2(0,0,0,2) Details
16956375 Leak RK, Liou AK, Zigmond MJ: Effect of sublethal 6-hydroxydopamine on the response to subsequent oxidative stress in dopaminergic cells: evidence for preconditioning. J Neurochem. 2006 Nov;99(4):1151-63. Epub 2006 Sep 4.

The antioxidant, N-acetyl cysteine (20 mM), when applied during preconditioning, abolished protection, as did the protein synthesis inhibitor, cycloheximide (0.2 microM).
Preconditioning rapidly increased phosphorylation of kinases ERK1/2, Akt and JNK, and was abolished by pharmacological inhibitors of their activity.
1(0,0,0,1) Details
17825525 Ray RM, Bhattacharya S, Johnson LR: EGFR plays a pivotal role in the regulation of polyamine-dependent apoptosis in intestinal epithelial cells. Cell Signal. 2007 Dec;19(12):2519-27. Epub 2007 Aug 15.


Phosphorylation of EGFR was concomitant with the activation of ERK1/2.
1(0,0,0,1) Details
16087789 Ishizawa K, Izawa Y, Ito H, Miki C, Miyata K, Fujita Y, Kanematsu Y, Tsuchiya K, Tamaki T, Nishiyama A, Yoshizumi M: Aldosterone stimulates vascular smooth muscle cell proliferation via big mitogen-activated protein kinase 1 activation. Hypertension. 2005 Oct;46(4):1046-52. Epub 2005 Aug 8.

Aldosterone-mediated phenomena were concluded to be attributable to a nongenomic effect because cycloheximide failed to inhibit aldosterone-induced BMK1 activation.
Aldosterone-induced nongenomic effects are attributable in part to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2), a classical mitogen-activated protein (MAP) kinase.
2(0,0,0,2) Details
16378625 Wu CC, Hsu MC, Hsieh CW, Lin JB, Lai PH, Wung BS: Upregulation of heme oxygenase-1 by Epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways. Life Sci. 2006 May 15;78(25):2889-97. Epub 2005 Dec 27.

Furthermore, EGCG-mediated HO-1 induction was abrogated in the presence of actinomycin D and cycloheximide, indicating that this upregulation of HO-1 occurred at the transcriptional level.
ECs treated with EGCG exhibit activation of Akt and ERK1/2.
2(0,0,0,2) Details
16040608 Verriere VA, Hynes D, Faherty S, Devaney J, Bousquet J, Harvey BJ, Urbach V: Rapid effects of dexamethasone on intracellular pH and Na+/H+ exchanger activity in human bronchial epithelial cells. J Biol Chem. 2005 Oct 28;280(43):35807-14. Epub 2005 Jul 22.

The rapid effect of dexamethasone on pH (i) was neither affected by the inhibitor of transcription, cycloheximide, nor by the classical glucocorticoid and mineralocorticoid receptors antagonists, RU486 and spironolactone, respectively.
The dexamethasone effect on pH (i) regulation was reduced by inhibitors of adenylate cyclase, cAMP-dependent protein kinase and mitogenactivated protein kinase (ERK1/2).
2(0,0,0,2) Details
16753025 Li CF, Hughes-Fulford M: Fibroblast growth factor-2 is an immediate-early gene induced by mechanical stress in osteogenic cells. J Bone Miner Res. 2006 Jun;21(6):946-55.

Pretreatment of MC3T3-E1 cells with cycloheximide showed that the induction of fgf-2 did not require new protein synthesis.
We have previously shown that physiological levels of MS in MC3T3-E1 cells causes extracellular signal-regulated kinase (ERK) 1/2 phosphorylation.
1(0,0,0,1) Details
16141313 Tian Q, Li J, Xie X, Sun M, Sang H, Zhou C, An T, Hu L, Ye RD, Wang MW: Stereospecific induction of nuclear factor-kappaB activation by isochamaejasmin. Mol Pharmacol. 2005 Dec;68(6):1534-42. Epub 2005 Sep 1.

Isochamaejasmin also induced time-dependent phosphorylation of the mitogen-activated protein kinases extracellular signal-regulated kinase 1/2 and p38, and a novel protein kinase C (PKCdelta).
It is noteworthy that the two stereoisomers and the methyl derivative did not induce detectable activation of NF-kappaB and were more cytotoxic than isochamaejasmin, which could partially rescue cycloheximide-induced apoptosis.
1(0,0,0,1) Details
16159906 Liu HS, Chen YH, Hung PF, Kao YH: Inhibitory effect of green tea (-)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway. Am J Physiol Endocrinol Metab. 2006 Feb;290(2):E273-81. Epub 2005 Sep 13.


Treatment with cycloheximide did not prevent EGCG-suppressed Rstn mRNA levels, which suggests that the effect of EGCG does not require new protein synthesis.
0(0,0,0,0) Details
17706224 Zhang W, Zhang Y, Edvinsson L, Xu CB: Up-regulation of thromboxane A2 receptor expression by lipid soluble smoking particles through post-transcriptional mechanisms. Atherosclerosis. 2008 Feb;196(2):608-16. Epub 2007 Aug 13.


This up-regulation was not affected by a general transcriptional inhibitor actinomycin D, but was almost completely abolished by cycloheximide, a general translational inhibitor.
0(0,0,0,0) Details
18599551 Wu ZY, Chen K, Haendler B, McDonald TV, Bian JS: Stimulation of N-terminal truncated isoform of androgen receptor stabilizes human ether-a-go-go-related gene-encoded potassium channel protein via activation of extracellular signal regulated kinase 1/2. Endocrinology. 2008 Oct;149(10):5061-9. Epub 2008 Jul 3.

Consistently, the cycloheximide-based protein chase study showed that 5alpha-DHT prolonged HERG protein half-life. 5alpha-DHT/AR45 signaling induced phosphorylation of ERK1/2.
84(1,1,1,4) Details
15561096 Rivedal E, Leithe E: Connexin43 synthesis, phosphorylation, and degradation in regulation of transient inhibition of gap junction intercellular communication by the phorbol ester TPA in rat liver epithelial cells. Exp Cell Res. 2005 Jan 15;302(2):143-52.

We show that coincubation of TPA with the protein synthesis inhibitor cycloheximide or the transcription inhibitor actinomycin D results in synergistic enhancement of the level of activated ERK1/2.
81(1,1,1,1) Details
16495213 Carraro-Lacroix LR, Ramirez MA, Zorn TM, Reboucas NA, Malnic G: Increased NHE1 expression is associated with serum deprivation-induced differentiation in immortalized rat proximal tubule cells. Am J Physiol Renal Physiol. 2006 Jul;291(1):F129-39. Epub 2006 Feb 21.


The altered activity of NHE1 was consistent with an increase of both transcription and translation of the antiporter, as the utilization of actinomycin D and cycloheximide significantly inhibited the upregulation of NHE1 induced by serum withdrawal.
0(0,0,0,0) Details
19286921 Croons V, Martinet W, Herman AG, Timmermans JP, De Meyer GR: The protein synthesis inhibitor anisomycin induces macrophage apoptosis in rabbit atherosclerotic plaques through p38 mitogen-activated protein kinase. J Pharmacol Exp Ther. 2009 Jun;329(3):856-64. Epub 2009 Mar 13.


We showed recently that the protein synthesis inhibitor cycloheximide, in contrast to puromycin, selectively depleted macrophages in rabbit atherosclerotic plaques without affecting smooth muscle cells (SMCs).
0(0,0,0,0) Details
19454725 Karahashi H, Michelsen KS, Arditi M: Lipopolysaccharide-induced apoptosis in transformed bovine brain endothelial cells and human dermal microvessel endothelial cells: the role of JNK. J Immunol. 2009 Jun 1;182(11):7280-6.


Stimulation of transformed bovine brain endothelial cells (TBBEC) with LPS leads to apoptosis while human microvessel endothelial cells (HMEC) need the presence of cycloheximide (CHX) with LPS to induce apoptosis.
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17916901 Keum YS, Chang PP, Kwon KH, Yuan X, Li W, Hu L, Kong AN: 3-Morpholinopropyl isothiocyanate is a novel synthetic isothiocyanate that strongly induces the antioxidant response element-dependent Nrf2-mediated detoxifying/antioxidant enzymes in vitro and in vivo. Carcinogenesis. 2008 Mar;29(3):594-9. Epub 2007 Oct 4.

Using chemical inhibitors of protein synthesis (cycloheximide) and 26S proteosomal degradation (MG-132), we observed that the induction of Nrf2 protein by 3MP-ITC appeared to be post-translationally regulated. 3MP-ITC activated ERK1/2 and JNK1/2 and the activation of antioxidant response element (ARE) by 3MP-ITC was significantly attenuated by chemical inhibition of PKC and PI3K signaling pathways in HepG2C8 cells.
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19684181 McEwen ST, Balus SF, Durand MJ, Lombard JH: Angiotensin II maintains cerebral vascular relaxation via EGF receptor transactivation and ERK1/2. Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1296-303. Epub 2009 Aug 14.

The protective effect of ANG II infusion to restore vascular relaxation was eliminated by coinfusion of either the EGF receptor kinase inhibitor AG-1478 (20 microg/h), the ERK1/2 inhibitor PD-98059 (10 microg/h), or the protein synthesis inhibitor cycloheximide (5 microg/h).
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18708082 Luo SF, Lin CC, Chen HC, Lin WN, Lee IT, Lee CW, Hsiao LD, Yang CM: Involvement of MAPKs, NF-kappaB and p300 co-activator in IL-1beta-induced cytosolic phospholipase A2 expression in canine tracheal smooth muscle cells. Toxicol Appl Pharmacol. 2008 Nov 1;232(3):396-407. Epub 2008 Jul 29.


IL-1beta-induced cPLA2 expression and PGE2 production was inhibited by actinomycin D and cycloheximide, indicating the involvement of transcriptional and translational events in these responses.
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18381294 Lin MT, Kuo IH, Chang CC, Chu CY, Chen HY, Lin BR, Sureshbabu M, Shih HJ, Kuo ML: Involvement of hypoxia-inducing factor-1alpha-dependent plasminogen activator inhibitor-1 up-regulation in Cyr61/CCN1-induced gastric cancer cell invasion. J Biol Chem. 2008 Jun 6;283(23):15807-15. Epub 2008 Apr 1.

Using cycloheximide and MG132, we demonstrated that the Cyr61-mediated HIF-1alpha up-regulation was through de novo protein synthesis, rather than increased protein stability. rCyr61 could also activate the PI3K/AKT/mTOR and ERK1/2 signaling pathways, both of which were essential for HIF-1alpha protein accumulation.
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16043662 Rude MK, Duhaney TA, Kuster GM, Judge S, Heo J, Colucci WS, Siwik DA, Sam F: Aldosterone stimulates matrix metalloproteinases and reactive oxygen species in adult rat ventricular cardiomyocytes. Hypertension. 2005 Sep;46(3):555-61. Epub 2005 Jul 25.


Aldosterone (50 nmol/L; 30 minutes) increased mitogen/extracellular signal-regulated kinase (MEK) (31+/-3%) and extracellular signal-regulated kinase 1/2 (ERK1/2; 41+/-7%; P <0.001 for both) phosphorylation.
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17081505 Paul S, Olausson P, Venkitaramani DV, Ruchkina I, Moran TD, Tronson N, Mills E, Hakim S, Salter MW, Taylor JR, Lombroso PJ: The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala. Biol Psychiatry. 2007 May 1;61(9):1049-61. Epub 2006 Nov 1.


METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation.
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18196969 Pyo JO, Nah J, Kim HJ, Lee HJ, Heo J, Lee H, Jung YK: Compensatory activation of ERK1/2 in Atg5-deficient mouse embryo fibroblasts suppresses oxidative stress-induced cell death. Autophagy. 2008 Apr 1;4(3):315-21. Epub 2008 Jan 7.

On the contrary, Atg5-/- MEFs were as sensitive to tumor necrosis factor (TNF)-alpha and cycloheximide as WT cells, and were more sensitive to cell death triggered by amino acid-deprivation than WT MEFs.
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16912191 Ma Y, Yu WD, Kong RX, Trump DL, Johnson CS: Role of nongenomic activation of phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase 1/2 pathways in 1,25D3-mediated apoptosis in squamous cell carcinoma cells. Cancer Res. 2006 Aug 15;66(16):8131-8.

These effects were nongenomic: they occurred rapidly and were not inhibited by cycloheximide or actinomycin D.
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15678124 Meller R, Stevens SL, Minami M, Cameron JA, King S, Rosenzweig H, Doyle K, Lessov NS, Simon RP, Stenzel-Poore MP: Neuroprotection by osteopontin in stroke. . J Cereb Blood Flow Metab. 2005 Feb;25(2):217-25.

Osteopontin treatment of cortical neuron cultures caused an increase in Akt and p42/p44 MAPK phosphorylation, which is consistent with OPN-inducing neuroprotection via the activation of these protein kinases.
The protective effect of OPN was also blocked by the protein synthesis inhibitor cycloheximide, suggesting that the neuroprotective effect of OPN required new protein synthesis.
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