Protein Information

Name PI3K
Synonyms GRB 1; PI3K; GRB1; PI3 kinase p85 subunit alpha; Phosphatidyl inositol 3 kinase associated p85 alpha; Phosphatidylinositol 3 kinase regulatory subunit alpha; PtdIns 3 kinase p85 alpha…

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
19457567 Jiang JX, Mikami K, Venugopal S, Li Y, Torok NJ: Apoptotic body engulfment by hepatic stellate cells promotes their survival by the JAK/STAT and Akt/NF-kappaB-dependent pathways. J Hepatol. 2009 Jul;51(1):139-48. Epub 2009 May 3.

The JAK/STAT- and PI3K/Akt-dependent pathways, NF-kappaB activation and expression of the anti-apoptotic proteins Mcl-1 and A1 were evaluated.
RESULTS: Phagocytosing HSC were resistant to FasL/cycloheximide or TRAIL-induced apoptosis.
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17804721 Endo H, Murata K, Mukai M, Ishikawa O, Inoue M: Activation of insulin-like growth factor signaling induces apoptotic cell death under prolonged hypoxia by enhancing endoplasmic reticulum stress response. Cancer Res. 2007 Sep 1;67(17):8095-103.

The cells were rescued from apoptosis when phosphatidylinositol 3-kinase (PI3K) or mTOR activity was inhibited, suggesting that these signals are critical in the observed cell death.
IGF-induced cell death under hypoxic conditions was prevented by treatment with cycloheximide, suggesting that de novo protein synthesis is required.
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17197193 Fritzenwanger M, Meusel K, Foerster M, Kuethe F, Krack A, Figulla HR: Cardiotrophin-1 induces interleukin-6 synthesis in human umbilical vein endothelial cells. Cytokine. 2006 Nov;36(3-4):101-6. Epub 2007 Jan 2.

For the pathway determination following inhibitors were used: piceatannol (signal transducer and activation of transcription (STAT) 3 phosphorylation), wortmannin (phosphatiylinositol 3-kinase (PI3K)), SB203580 (p38 mitogen-activated protein kinase (MAPK)), AG490 (Janus kinase (JAK) 2), PD98059 (mitogen-activated protein kinase kinase (MEK) 1/2), parthenolide (nuclear factor kappaB) and cycloheximide (protein biosynthesis).
81(1,1,1,1) Details
18540098 Kawauchi K, Tobiume K, Iwashita K, Inagaki H, Morikawa T, Shibukawa Y, Moriyama Y, Hirata H, Kamata H: Cycloprodigiosin hydrochloride activates the Ras-PI3K-Akt pathway and suppresses protein synthesis inhibition-induced apoptosis in PC12 cells. Biosci Biotechnol Biochem. 2008 Jun;72(6):1564-70. Epub 2008 Jun 7.

In this study, we found a novel function of cPrG-HCl; to suppress cell death in PC12 cells, which is caused by protein synthesis inhibitors cycloheximide and actinomycin D. cPrG-HCl activated Akt and suppressed apoptosis, and this was accompanied by inhibition of caspase-3 activity and DNA fragmentation independently of its H (+)/Cl (-) symporter activity.
1(0,0,0,1) Details
16859513 Shapira M, Kakiashvili E, Rosenberg T, Hershko DD: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells. Breast Cancer Res. 2006;8(4):R46.

The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer.
The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1.
1(0,0,0,1) Details
16034134 Grehan JF, Levay-Young BK, Fogelson JL, Francois-Bongarcon V, Benson BA, Dalmasso AP: IL-4 and IL-13 induce protection of porcine endothelial cells from killing by human complement and from apoptosis through activation of a phosphatidylinositide 3-kinase/Akt pathway. J Immunol. 2005 Aug 1;175(3):1903-10.

We conclude that IL-4 and IL-13 can induce protection of porcine EC against killing by apoptosis and human complement through activation of the PI3K/Akt signaling pathway.
We found that porcine EC incubated with IL-4 or IL-13, but not with IL-10 or IL-11, became protected from killing by complement and apoptosis induced by TNF-alpha plus cycloheximide.
1(0,0,0,1) Details
15801978 Shirk AJ, Kuver R: Epidermal growth factor mediates detachment from and invasion through collagen I and Matrigel in Capan-1 pancreatic cancer cells. BMC Gastroenterol. 2005 Mar 31;5:12.

EGF receptor signalling involving the erbB2 and PI3K pathways plays a role in mediating these events in Capan-1 cells.
The loss of adhesion was reversed by AG825, an inhibitor of erbB2 receptor signalling and by wortmannin, a PI3K inhibitor, but not by the protein synthesis inhibitor cycloheximide.
1(0,0,0,1) Details
18501893 Zeigerer A, Rodeheffer MS, McGraw TE, Friedman JM: Insulin regulates leptin secretion from 3T3-L1 adipocytes by a PI 3 kinase independent mechanism. Exp Cell Res. 2008 Jul 1;314(11-12):2249-56. Epub 2008 Apr 12.


These studies show that insulin can stimulate leptin release via a PI3K independent mechanism and provide a cellular system for studying the effect of insulin and potentially other mediators on leptin secretion.
1(0,0,0,1) Details
16245312 Jinnin M, Ihn H, Asano Y, Yamane K, Trojanowska M, Tamaki K: Platelet derived growth factor induced tenascin-C transcription is phosphoinositide 3-kinase/Akt-dependent and mediated by Ets family transcription factors. J Cell Physiol. 2006 Mar;206(3):718-27.

Actinomycin D, an RNA synthesis inhibitor, significantly blocked the PDGF-mediated upregulation of TN-C mRNA expression, whereas cycloheximide, a protein synthesis inhibitor, did not.
The PDGF-mediated induction of TN-C expression was inhibited by the treatment of fibroblasts with a selective phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, or LY294002.
1(0,0,0,1) Details
15743808 Bader AG, Vogt PK: Inhibition of protein synthesis by Y box-binding protein 1 blocks oncogenic cell transformation. Mol Cell Biol. 2005 Mar;25(6):2095-106.


The multifunctional Y box-binding protein 1 (YB-1) is transcriptionally repressed by the oncogenic phosphoinositide 3-kinase (PI3K) pathway (with P3K as an oncogenic homolog of the catalytic subunit) and, when reexpressed with the retroviral vector RCAS, interferes with P3K- and Akt-induced transformation of chicken embryo fibroblasts.
1(0,0,0,1) Details
19006119 Suh HN, Lee YJ, Han HJ: Interleukin-6 promotes 2-deoxyglucose uptake through p44/42 MAPKs activation via Ca2+/PKC and EGF receptor in primary cultured chicken hepatocytes. J Cell Physiol. 2009 Mar;218(3):643-52.

Indeed, IL-6 increased GLUT-2 mRNA and protein expression as well as 2-DG uptake, which were blocked by actinomycin D (AD, transcription inhibitor) and cycloheximide (CHX, translation inhibitor).
In addition, IL-6 increased EGFR/src/FAK, PI3K/Akt phosphorylation and 2-DG uptake as well as GLUT-2 protein expression, which were blocked by AG 1478 (EGF receptor inhibitor), PP2 (src family of tyrosine kinase inhibitor), PI3K-specific siRNA, and a Akt inhibitor.
1(0,0,0,1) Details
17015939 Purintrapiban J, Suttajit M, Forsberg NE: Differential activation of glucose transport in cultured muscle cells by polyphenolic compounds from Canna indica L. Biol Pharm Bull. 2006 Oct;29(10):1995-8.

Our findings suggest that GLUT1 protein synthesis and the activation of phosphatidylinositol 3-kinase (PI3K) are critical for the increase in glucose transporter activity at the plasma membrane and essential for the maximal induction of glucose transport by CI in L8 muscle cells.
Cycloheximide treatment almost completely reversed CI-induced 2-DG uptake to the basal level.
1(0,0,0,1) Details
16123394 Kim KU, Wilson SM, Abayasiriwardana KS, Collins R, Fjellbirkeland L, Xu Z, Jablons DM, Nishimura SL, Broaddus VC: A novel in vitro model of human mesothelioma for studying tumor biology and apoptotic resistance. Am J Respir Cell Mol Biol. 2005 Dec;33(6):541-8. Epub 2005 Aug 25.

Apoptotic resistance of mesothelioma cells was significantly reduced by inhibiting either the PI3K/Akt pathway with LY294002 (47 +/- 6% apoptosis) or the mTOR pathway with rapamycin (50 +/- 17% apoptosis).
To determine responses to treatment, we treated tumor fragment spheroids grown from three separate tumors with agents, TNF-related apoptosis-inducing ligand (TRAIL) plus cycloheximide, that induced near total apoptosis in three human mesothelioma cell lines (M28, REN, MS-1) grown as monolayers (94 +/- 6% apoptosis; mean +/- SEM).
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17495535 Lee SH, Lee SJ, Kim JH, Park BJ: Chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine, is a specific activator of oncogenic Ras. Cell Cycle. 2007 May 15;6(10):1257-64. Epub 2007 May 6.


Activation of Erk by MNNG could not suppressed by cycloheximide and ALLN.
0(0,0,0,0) Details
18655183 Lee DH, Lee YJ: Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis. J Cell Biochem. 2008 Oct 1;105(2):546-53.


Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia.
0(0,0,0,0) Details
16951370 Rahman MS, Yamasaki A, Yang J, Shan L, Halayko AJ, Gounni AS: IL-17A induces eotaxin-1/CC chemokine ligand 11 expression in human airway smooth muscle cells: role of MAPK (Erk1/2, JNK, and p38) pathways. J Immunol. 2006 Sep 15;177(6):4064-71.


Moreover, IL-17A significantly induced eotaxin-1/CCL11 release and mRNA expression, an effect that was abrogated with cycloheximide and actinomycin D treatment.
0(0,0,0,0) Details
17537394 Podgorska M, Kocbuch K, Grden M, Szulc A, Szutowicz A, Pawelczyk T: Different signaling pathways utilized by insulin to regulate the expression of ENT2, CNT1, CNT2 nucleoside transporters in rat cardiac fibroblasts. Arch Biochem Biophys. 2007 Aug 15;464(2):344-9. Epub 2007 May 11.


The insulin-induced increase of the ENT2 mRNA level was blocked by rapamycin (an inhibitor of mTOR) and by cycloheximide (an inhibitor of protein synthesis), whereas neither wortmannin (an inhibitor of PI3K) nor PD98059 (an inhibitor of MEK) affected the insulin action on the ENT2 transcript level.
0(0,0,0,0) Details
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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16251184 Almeida M, Han L, Bellido T, Manolagas SC, Kousteni S: Wnt proteins prevent apoptosis of both uncommitted osteoblast progenitors and differentiated osteoblasts by beta-catenin-dependent and -independent signaling cascades involving Src/ERK and phosphatidylinositol 3-kinase/AKT. J Biol Chem. 2005 Dec 16;280(50):41342-51. Epub 2005 Oct 25.

The anti-apoptotic effect of Wnt3a was abrogated by inhibitors of canonical Wnt signaling, as well as by inhibitors of MEK, Src, phosphatidylinositol 3-kinase (PI3K), or Akt kinases, or by the addition of cycloheximide to the culture medium.
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15695798 Paik JY, Lee KH, Ko BH, Choe YS, Choi Y, Kim BT: Nitric oxide stimulates 18F-FDG uptake in human endothelial cells through increased hexokinase activity and GLUT1 expression. J Nucl Med. 2005 Feb;46(2):365-70.

SNP-stimulated (18) F-FDG uptake was abolished by cotreatment with cycloheximide, the tyrosine kinase inhibitor genistein, the phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin, or the protein kinase C inhibitor staurosporine.
31(0,1,1,1) Details
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.
31(0,1,1,1) Details
15728510 Molnarfi N, Hyka-Nouspikel N, Gruaz L, Dayer JM, Burger D: The production of IL-1 receptor antagonist in IFN-beta-stimulated human monocytes depends on the activation of phosphatidylinositol 3-kinase but not of STAT1. J Immunol. 2005 Mar 1;174(5):2974-80.

The use of cycloheximide and actinomycin D shows that sIL-1Ra was an immediate early gene induced by IFN-beta and that PI3K was controlling sIL-1Ra gene transcription.
9(0,0,1,4) Details
18762555 Kogai T, Sajid-Crockett S, Newmarch LS, Liu YY, Brent GA: Phosphoinositide-3-kinase inhibition induces sodium/iodide symporter expression in rat thyroid cells and human papillary thyroid cancer cells. J Endocrinol. 2008 Nov;199(2):243-52. Epub 2008 Sep 1.

Activation of the insulin/phosphoinositide-3-kinase (PI3K) signaling pathway in TSH-stimulated thyroid cells reduces NIS expression at the transcriptional level.
The induction of Nis mRNA by LY294002 occurred 6 h after treatment, and was abolished by a translation inhibitor, cycloheximide.
7(0,0,0,7) Details
16433909 Clotworthy M, Traynor D: On the effects of cycloheximide on cell motility and polarisation in Dictyostelium discoideum. BMC Cell Biol. 2006 Jan 24;7:5.

In the presence of cycloheximide, aggregation-competent amoebae sensitive to cAMP, although round, can still localise CRAC, ABP120, PI3K and actin polymerisation in response to a micropipette filled with cAMP.
6(0,0,1,1) Details
16051672 Moeller LC, Dumitrescu AM, Refetoff S: Cytosolic action of thyroid hormone leads to induction of hypoxia-inducible factor-1alpha and glycolytic genes. Mol Endocrinol. 2005 Dec;19(12):2955-63. Epub 2005 Jul 28.


HIF-1alpha expression and activity can be regulated through phosphatidylinositol-OH-3-kinase (PI3K) and MAPK signaling; thus the possibility of alternative, nonnuclear pathways of TH action was raised.
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17407140 Fu Y, Fang Z, Liang Y, Zhu X, Prins P, Li Z, Wang L, Sun L, Jin J, Yang Y, Zha X: Overexpression of integrin beta1 inhibits proliferation of hepatocellular carcinoma cell SMMC-7721 through preventing Skp2-dependent degradation of p27 via PI3K pathway. J Cell Biochem. 2007 Oct 15;102(3):704-18.

Cycloheximide (Chx) treatment and pulse-chase experiments revealed that overexpression of integrin beta1 prolonged the half-life of p27 (Kip1) by inhibiting its degradation.
4(0,0,0,4) Details
18511708 Wilson SM, Barbone D, Yang TM, Jablons DM, Bueno R, Sugarbaker DJ, Nishimura SL, Gordon GJ, Broaddus VC: mTOR mediates survival signals in malignant mesothelioma grown as tumor fragment spheroids. Am J Respir Cell Mol Biol. 2008 Nov;39(5):576-83. Epub 2008 May 29.


Solid tumors such as mesothelioma exhibit a stubborn resistance to apoptosis that may derive from survival pathways, such as PI3K/Akt/mTOR, that are activated in many tumors, including mesothelioma.
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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.

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.
3(0,0,0,3) Details
17557191 Shen J, Jiang J, Wei Y, Zhou L, Liu D, Zhou J, Gu J: Two specific inhibitors of the phosphatidylinositol 3-kinase LY294002 and wortmannin up-regulate beta1,4-galactosyltransferase I and thus sensitize SMMC-7721 human hepatocarcinoma cells to cycloheximide-induced apoptosis. Mol Cell Biochem. 2007 Oct;304(1-2):361-7. Epub 2007 Jun 8.

However, the two PI3K inhibitors LY294002 and wortmannin treatment up-regulated beta1,4GT1 through enhancing Sp1 protein expression and consequently increased CHX-induced SMMC-7721 cells apoptosis.
3(0,0,0,3) 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.
To investigate the molecular mechanism of LPS-induced apoptosis in HMEC or TBBEC, we analyzed the involvement of MAPK and PI3K in TBBEC and HMEC.
3(0,0,0,3) Details
15642371 Schnitzer SE, Schmid T, Zhou J, Eisenbrand G, Brune B: Inhibition of GSK3beta by indirubins restores HIF-1alpha accumulation under prolonged periods of hypoxia/anoxia. FEBS Lett. 2005 Jan 17;579(2):529-33.


HIF-1alpha is subjected to proteasomal destruction or enhanced protein translation, which requires the phosphatidylinositol 3-kinase (PI3K)/Akt pathway.
3(0,0,0,3) Details
19188658 Kulasekaran P, Scavone CA, Rogers DS, Arenberg DA, Thannickal VJ, Horowitz JC: Endothelin-1 and transforming growth factor-beta1 independently induce fibroblast resistance to apoptosis via AKT activation. Am J Respir Cell Mol Biol. 2009 Oct;41(4):484-93. Epub 2009 Feb 2.


ET-1 rapidly activates the prosurvival phosphatidylinositol 3'-OH kinase (PI3K)/AKT signaling pathway in normal and fibrotic human lung fibroblasts.
2(0,0,0,2) Details
20352620 Lorente-Cebrian S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ: Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes. Mol Nutr Food Res. 2010 Mar 29.

EPA also stimulated Akt phosphorylation, a down-stream target of phosphatidylinositol 3-kinase (PI3K), in 3T3-L1 adipocytes.
Furthermore, the stimulatory effect of EPA on basal apelin release was also observed in the presence of Actinomycin D and Cycloheximide, suggesting that EPA might also regulate apelin secretion by via post-transcriptional mechanisms.
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16817231 Siri S, Chen MJ, Chen TT: Biological activity of rainbow trout Ea4-peptide of the pro-insulin-like growth factor (pro-IGF)-I on promoting attachment of breast cancer cells (MDA-MB-231) via alpha2- and beta1-integrin. J Cell Biochem. 2006 Dec 15;99(6):1524-35.

Expression of fibronectin 1 gene induced by rtEa4-peptide in MDA-MB-231 cells was abolished by inhibitors of PI3K, PKC, Mek1/2, JNK1/2, and p38 MAPK signaling transduction molecules.
Blocking new protein synthesis by cycloheximide significantly reduced the attachment of MDA-MB-231 cells to rtEa4-peptide coated wells by 50%.
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18303854 Zanatta L, Rosso A, Folador P, Figueiredo MS, Pizzolatti MG, Leite LD, Silva FR: Insulinomimetic effect of kaempferol 3-neohesperidoside on the rat soleus muscle. J Nat Prod. 2008 Apr;71(4):532-5. Epub 2008 Feb 28.

The effect of 1 on glucose uptake was completely nullified by pretreatment with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), and RO318220, an inhibitor of protein kinase C (PKC).
However, no significant change occurred on glucose uptake stimulated by 1 when muscles were pretreated with PD98059, an inhibitor of mitogen-activated protein kinase (MEK), and cycloheximide, an inhibitor of protein synthesis.
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19193945 Soria LR, Gradilone SA, Larocca MC, Marinelli RA: Glucagon induces the gene expression of aquaporin-8 but not that of aquaporin-9 water channels in the rat hepatocyte. Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1274-81. Epub 2009 Feb 4.

Cycloheximide also showed no effect, suggesting that glucagon-induced AQP8 expression does not depend on protein synthesis but rather on protein degradation.
The action of glucagon on hepatocyte AQP8 was mimicked by dibutyryl cAMP and suppressed by PKA or phosphatidylinositol-3-kinase (PI3K) inhibitors.
2(0,0,0,2) Details
16870142 Yamada T, Ozaki N, Kato Y, Miura Y, Oiso Y: Insulin downregulates angiopoietin-like protein 4 mRNA in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2006 Sep 8;347(4):1138-44. Epub 2006 Jul 17.


Insulin suppressed angptl4 mRNA expression in time- and dose-dependent manners, and the inhibitory effect was attenuated by a RNA synthesis inhibitor actinomycin D and a phosphoinositide 3-kinase (PI3K) inhibitor LY294002.
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19396617 Carraro-Lacroix LR, Girardi AC, Malnic G: Long-term regulation of vacuolar H (+)-ATPase by angiotensin II in proximal tubule cells. Pflugers Arch. 2009 Sep;458(5):969-79. Epub 2009 Apr 26.


Inhibition of phosphatidylinositol-3-kinase (PI3K) by wortmannin and of p38 mitogen-activated protein kinase (MAPK) by SB 203580 also blocked this effect.
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18638274 Shao H, Yi XM, Wells A: Epidermal growth factor protects fibroblasts from apoptosis via PI3 kinase and Rac signaling pathways. Wound Repair Regen. 2008 Jul-Aug;16(4):551-8.

The survival effect of EGF on rescuing apoptotic NR6WT involves signaling pathways that derive from PI3K and Rac; the blockade of apoptosis is abolished when PI3K and Rac signals are inhibited simultaneously.
Interestingly, EGF prevention of apoptosis induced by tumor necrosis factor-alpha in the face of cycloheximide blockade of protein translation occurs via a different set of pathways as the simultaneous inhibition of extracellular signal-regulated kinase, Rac, and PI3K signaling did not eliminate EGF from rescuing fibroblasts in the face of this cytokine.
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18565131 Arayatrakoollikit U, Pavasant P, Yongchaitrakul T: Thrombin induces osteoprotegerin synthesis via phosphatidylinositol 3'-kinase/mammalian target of rapamycin pathway in human periodontal ligament cells. J Periodontal Res. 2008 Oct;43(5):537-43. Epub 2008 Jun 28.

The phosphatidylinositol 3'-kinase (PI3K) inhibitor, LY294002, and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exerted an inhibitory effect on the thrombin-induced OPG synthesis.
The inductive effect was inhibited by cycloheximide, but not by indomethacin.
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17331500 Bian ZM, Elner SG, Elner VM: Regulation of VEGF mRNA expression and protein secretion by TGF-beta2 in human retinal pigment epithelial cells. Exp Eye Res. 2007 May;84(5):812-22. Epub 2007 Jan 9.

Moreover, TGF-beta2-induced RPE VEGF secretion was significantly reduced by inhibitors of mitogen-activated protein (MAP) kinase (MEK) (U0126), p38 (SB202190), c-Jun NH2-terminal kinase (JNK), Sp600125, protein tyrosine kinase (PTK) (Genistein), and phosphatidylinositol 3-kinase (PI3K) (Ly294002).
Stimulation of VEGF expression by TGF-beta2 was blocked by cycloheximide, suggesting that de novo protein synthesis is required.
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19254925 Maeda T, Horiuchi N: Simvastatin suppresses leptin expression in 3T3-L1 adipocytes via activation of the cyclic AMP-PKA pathway induced by inhibition of protein prenylation. J Biochem. 2009 Jun;145(6):771-81. Epub 2009 Mar 2.

Treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002 and wortmannin, reduced leptin expression in 3T3-L1 cells.
Simvastatin inhibition of leptin gene transcription was not abrogated by pre-treatment with cycloheximide, an inhibitor of protein synthesis.
2(0,0,0,2) Details
19070612 Cazarolli LH, Folador P, Moresco HH, Brighente IM, Pizzolatti MG, Silva FR: Mechanism of action of the stimulatory effect of apigenin-6-C-(2''-O-alpha-l-rhamnopyranosyl)-beta-L-fucopyranoside on 14C-glucose uptake. Chem Biol Interact. 2009 May 15;179(2-3):407-12. Epub 2008 Nov 25.

The effect of compound 1 on glucose uptake was completely nullified by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK), cycloheximide, an inhibitor of protein synthesis, and colchicine, a microtubule-depolymerizing agent.
The effect of compound 1 on glucose uptake was completely nullified by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK), cycloheximide, an inhibitor of protein synthesis, and colchicine, a microtubule-depolymerizing agent.
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17683115 Fernandez N, Gonzalez A, Valera I, Alonso S, Crespo MS: Mannan and peptidoglycan induce COX-2 protein in human PMN via the mammalian target of rapamycin. Eur J Immunol. 2007 Sep;37(9):2572-82.

Treatment with the phosphatidylinositol 3-kinase inhibitor (PI3K) wortmaninn, the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and the translation inhibitor cycloheximide blocked the induction of COX-2 protein in response to mannan and PGN, whereas the transcriptional inhibitor actinomycin D did not show a significant effect.
These results disclose a capability of pathogen-associated molecular patterns to induce the oxidative metabolism of arachidonic acid more robust than that of PMN archetypal chemoattractants, since mannan and PGN make it coincidental the release of arachidonic acid with a rapid induction of COX-2 protein regulated by a signaling cascade involving PI3K, mTOR, and the translation machinery.
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