Protein Information

Name protein kinase C (protein family or complex)
Synonyms Protein kinase C; PKC

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
18187554 Yang D, Guo J, Divieti P, Shioda T, Bringhurst FR: CBP/p300-interacting protein CITED1 modulates parathyroid hormone regulation of osteoblastic differentiation. Endocrinology. 2008 Apr;149(4):1728-35. Epub 2008 Jan 10.

Stimulation of CITED1 mRNA by PTH was transient, peaking at 4 h, concentration dependent, and blocked by actinomycin D but not cycloheximide.
The stimulation was mimicked by forskolin, phorbol ester, and the cAMP-selective PTH analog [G (1),R (19)] hPTH (1-28) and inhibited completely by the protein kinase A inhibitor, H89 and partially by phorbol ester-induced protein kinase C depletion.
1(0,0,0,1) Details
17064352 Bobrovskaya L, Gilligan C, Bolster EK, Flaherty JJ, Dickson PW, Dunkley PR: Sustained phosphorylation of tyrosine hydroxylase at serine 40: a novel mechanism for maintenance of catecholamine synthesis. J Neurochem. 2007 Jan;100(2):479-89. Epub 2006 Oct 25.


The protein kinase (s) responsible for TH phosphorylation at Ser40 switched from being protein kinase C (PKC) independent in the acute phase to PKC dependent in the sustained phase.
1(0,0,0,1) Details
17178924 Moreau ME, Bawolak MT, Morissette G, Adam A, Marceau F: Role of nuclear factor-kappaB and protein kinase C signaling in the expression of the kinin B1 receptor in human vascular smooth muscle cells. Mol Pharmacol. 2007 Mar;71(3):949-56. Epub 2006 Dec 18.

Various stimulatory compounds that increase receptor mRNA stability only (human and bovine sera, cycloheximide) or that stimulate NF-kappaB nuclear translocation and both mRNA concentration and stability [interleukin (IL)-1beta, phorbol 12-myristate 13-acetate (PMA)] all increased the density of binding sites for the tritiated B1 receptor agonist [3H] Lys-des-Arg9-bradykinin (without change in receptor affinity) in cell-based assays.
4(0,0,0,4) Details
15770661 Wang HS, Tung WH, Tang KT, Wong YK, Huang GJ, Wu JC, Guo YJ, Chen CC: TGF-beta induced hyaluronan synthesis in orbital fibroblasts involves protein kinase C betaII activation in vitro. J Cell Biochem. 2005 May 15;95(2):256-67.

Stimulation by TGF-beta and PMA were dependent on protein synthesis and their effects were inhibited by cycloheximide.
1(0,0,0,1) Details
20339915 Ji L, Chauhan A, Chauhan V: Calcium Induces Expression of Cytoplasmic Gelsolin in SH-SY5Y and HEK-293 Cells. Neurochem Res. 2010 Mar 26.

We report here that calcium ionophore A23187 induces the expression of cytoplasmic gelsolin (c-gelsolin), and that protein kinase C (PKC) is involved in the up-regulation of c-gelsolin.
Calcium-mediated up-regulation of c-gelsolin was inhibited by cycloheximide (a general inhibitor of protein synthesis).
1(0,0,0,1) Details
17143556 Lai YL, Yamaguchi M: Phytocomponent p-hydroxycinnamic acid inhibits osteoclast-like cell formation in mouse bone marrow cultures. Int J Mol Med. 2007 Jan;19(1):123-8.

The inhibitory effect of HCA (10 (-6) or 10 (-5) M) on RANKL plus M-CSF-induced osteoclast-like cell formation was not observed in the presence of cycloheximide (10 (-7) M), an inhibitor of protein synthesis in the transcriptional process, or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (10 (-6) M), an inhibitor of transcription.
HCA (10 (-6) or 10 (-5) M) significantly inhibited osteoclast-like cell formation induced by dibutyryl cyclic adenosine monophosphate (10 (-5) M) or phorbol 12-myristate 13-acetate (10 (-6) M), an activator of protein kinase C.
1(0,0,0,1) Details
16888033 Garcia CS, Curiel RE, Mwatibo JM, Pestka S, Li H, Espinoza-Delgado I: The antineoplastic agent bryostatin-1 differentially regulates IFN-gamma receptor subunits in monocytic cells: transcriptional and posttranscriptional control of IFN-gamma R2. J Immunol. 2006 Aug 15;177(4):2707-16.

Bryostatin-1 (Bryo-1) is a potent ligand and modulator of protein kinase C that exerts antineoplastic and immunomodulatory activities both in vitro and in vivo.
Bryo-1-induced up-regulation of IFN-gammaR2 mRNA levels is not dependent on de novo protein synthesis as shown by cell treatment with the protein-synthesis inhibitor cycloheximide.
1(0,0,0,1) Details
19376214 Ridley W, Matsuoka M: Fluoride-induced cyclooxygenase-2 expression and prostaglandin E2 production in A549 human pulmonary epithelial cells. Toxicol Lett. 2009 Aug 10;188(3):180-5. Epub 2009 Apr 17.

NaF-induced accumulation of COX-2 transcript was abolished by actinomycin D, but not cycloheximide.
Phosphorylated forms of mitogen-activated protein kinases (MAPKs)-including extracellular signal-regulated protein kinase (ERK), c-Jun NH (2)-terminal kinase, and p38-increased after NaF exposure, while treatment with the MAPK/ERK kinase inhibitor U0126 and the p38 inhibitor SB203580 markedly suppressed COX-2 expression.
1(0,0,0,1) Details
15944291 Wojciechowski W, Li H, Marshall S, Dell'Agnola C, Espinoza-Delgado I: Enhanced expression of CD20 in human tumor B cells is controlled through ERK-dependent mechanisms. J Immunol. 2005 Jun 15;174(12):7859-68.


The effect of bryostatin-1 on CD20 expression in non-Hodgkin's lymphoma cells was mediated through the MAPK kinase/ERK signal transduction pathway and involved protein kinase C, but was independent of p38 MAPK and was insensitive to dexamethasone.
1(0,0,0,1) Details
17266789 Toranzo GS, Bonilla F, Zelarayan L, Oterino J, Buhler MI: Activation of maturation promoting factor in Bufo arenarum oocytes: injection of mature cytoplasm and germinal vesicle contents. Zygote. 2006 Nov;14(4):305-16.


The injection of cytoplasm containing active MPF is sufficient to activate an amplification loop that requires the activation of cdc25 and protein kinase C, the decrease in cAMP levels, and is independent of protein synthesis.
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
17329956 Matsumoto E, Hatanaka M, Bohgaki M, Maeda S: PKC pathway and ERK/MAPK pathway are required for induction of cyclin D1 and p21Waf1 during 12-o-tetradecanoylphorbol 13-acetate-induced differentiation of myeloleukemia cells. Kobe J Med Sci. 2006;52(6):181-94.


Induction of cyclin D1 expression in TPA-treated HL60 cells was inhibited with protein kinase C (PKC) inhibitor bisindolylmaleimide I and mitogen activated protein kinase kinase (MEK) inhibitor PD98059.
1(0,0,0,1) Details
16571380 Huwiler A, Doll F, Ren S, Klawitter S, Greening A, Romer I, Bubnova S, Reinsberg L, Pfeilschifter J: Histamine increases sphingosine kinase-1 expression and activity in the human arterial endothelial cell line EA.hy 926 by a PKC-alpha-dependent mechanism. Biochim Biophys Acta. 2006 Mar;1761(3):367-76. Epub 2006 Mar 10.

A similar upregulation of SK-1 is also observed with the direct protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA).
The increased SK-1 protein expression is due to stimulated de novo synthesis since cycloheximide inhibited the delayed SK-1 protein upregulation.
1(0,0,0,1) Details
15654655 Sabbieti MG, Marchetti L, Gabrielli MG, Menghi M, Materazzi S, Menghi G, Raisz LG, Hurley MM: Prostaglandins differently regulate FGF-2 and FGF receptor expression and induce nuclear translocation in osteoblasts via MAPK kinase. Cell Tissue Res. 2005 Feb;319(2):267-78. Epub 2004 Dec 10.

Pre-treatment with cycloheximide blocks nuclear labelling for FGF-2 in response to PGF (2alpha).
Similar results are obtained by pre-treatment with the protein kinase C (PKC) inhibitor H-7.
1(0,0,0,1) Details
15946695 Han HJ, Heo JS, Lee YJ: ANG II increases 2-deoxyglucose uptake in mouse embryonic stem cells. . Life Sci. 2005 Aug 26;77(15):1916-33.

Actinomycin D and cycloheximide completely blocked the effect of ANG II on 2-DG uptake.
Protein kinase C (PKC) inhibitors, staurosporine, bisindolylmaleimide I, and H-7 also blocked ANG II-induced stimulation of 2-DG uptake.
1(0,0,0,1) Details
16433893 Cao YX, Xu CB, Luo GG, Edvinsson L: Up-regulation of alpha1A-adrenoceptors in rat mesenteric artery involves intracellular signal pathways. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):61-7.

Transcriptional inhibitor actinomycin D, translational inhibitor cycloheximide, protein kinase C inhibitors (staurosporine and RO31-8220) and mitogen-activated protein kinase (MAPK) pathway inhibitors (SB386023, U0126 and SB239063) prevented the increase in NA-induced contractions.
32(0,1,1,2) Details
16297161 Hormdee D, Nagasawa T, Kiji M, Yashiro R, Kobayashi H, Koshy G, Noguchi K, Nitta H, Ishikawa I: Protein kinase-A-dependent osteoprotegerin production on interleukin-1 stimulation in human gingival fibroblasts is distinct from periodontal ligament fibroblasts. Clin Exp Immunol. 2005 Dec;142(3):490-7.

Human gingival fibroblasts (HGF) and periodontal ligament fibroblasts (PDL) were stimulated with IL-1alpha with or without protein synthesis inhibitor cycloheximide (CHX), protein kinase A (PKA) inhibitors, protein kinase C (PKC) inhibitors and prostaglandin E (2) (PGE (2)) inhibitor.
31(0,1,1,1) Details
18948121 Lim SK, Park MJ, Jung HK, Park AY, Kim DI, Kim JC, Bae CS, Kim KY, Yoon KC, Han HJ, Park SH: Bradykinin stimulates glutamate uptake via both B1R and B2R activation in a human retinal pigment epithelial cells. Life Sci. 2008 Dec 5;83(23-24):761-70. Epub 2008 Sep 30.


Furthermore, the BK-induced increase in COX-2 expression was blocked by the PI-3 kinase inhibitors wortmannin and LY294002, Akt inhibitor, and the protein kinase C (PKC) inhibitors staurosporine and bisindolylmaleimide I, suggesting the role of PI-3 kinase and PKC in this process.
1(0,0,0,1) Details
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.

Induced VEGF expression was completely abrogated by inhibitors of protein kinase C (PKC) (Ro318220), nuclear factor-kappaB (NF-kappaB) [caffeic acid phenethyl ester (CAPE)], and reactive oxygen species (ROS) [N-acetyl-cysteine (Nac) and diphenyleneiodonium (DPI)].
Stimulation of VEGF expression by TGF-beta2 was blocked by cycloheximide, suggesting that de novo protein synthesis is required.
1(0,0,0,1) Details
19843871 Qi D, Cai K, Wang O, Li Z, Chen J, Deng B, Qian L, Le Y: Fatty acids induce amylin expression and secretion by pancreatic {beta}-cells. Am J Physiol Endocrinol Metab. 2009 Oct 20.

Pretreatment of MIN6 cells with Ca (2+) chelator (EGTA, BAPTA/AM), protein kinase C (PKC) inhibitor Go6976, or protein synthesis inhibitor cycloheximide significantly inhibited FA-induced amylin mRNA expression.
31(0,1,1,1) Details
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
17885094 Canas N, Valero T, Villarroya M, Montell E, Verges J, Garcia AG, Lopez MG: Chondroitin sulfate protects SH-SY5Y cells from oxidative stress by inducing heme oxygenase-1 via phosphatidylinositol 3-kinase/Akt. J Pharmacol Exp Ther. 2007 Dec;323(3):946-53. Epub 2007 Sep 20.

Taken together, these results show that CS can protect SH-SY5Y cells under oxidative stress conditions by activating protein kinase C, which phosphorylates Akt that, via the phosphatidylinositol 3-kinase/Akt pathway, induces the synthesis of the antioxidant protein heme oxygenase-1.
The protective effects of CS were prevented by chelerythrine, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), cycloheximide, and Sn (IV)-protoporphyrin IX.
1(0,0,0,1) Details
16543731 Heo JS, Han HJ: PKC and MAPKs pathways mediate EGF-induced stimulation of 2-deoxyglucose uptake in mouse embryonic stem cells. Cell Physiol Biochem. 2006;17(3-4):145-58. Epub 2006 Mar 14.

Actinomycin D and cycloheximide completely blocked the effect of EGF on 2-DG uptake.
In addition, EGF effect was blocked by neomycin and U 73122 [phospholipase C (PLC) inhibitors] as well as staurosporine and bisindolylmaleimide I [protein kinase C (PKC) inhibitors].
1(0,0,0,1) Details
17065529 Tezel TH, Geng L, Kaplan HJ, Del Priore LV: Retinal pigment epithelium rescues vascular endothelium from retinoic acid-induced apoptosis. Invest Ophthalmol Vis Sci. 2006 Nov;47(11):5075-87.

Apoptosis rates were determined at 24 hours, and the effect of inhibition of protein synthesis and activation of protein kinase C on apoptosis was investigated by supplying culture medium with 0.1 mg/mL cycloheximide and 10 nM phorbol myristate acetate.
31(0,1,1,1) Details
18479958 Lee MY, Han HJ: Galectin-1 upregulates glucose transporter-1 expression level via protein kinase C, phosphoinositol-3 kinase, and mammalian target of rapamycin pathways in mouse embryonic stem cells. Int J Biochem Cell Biol. 2008;40(11):2421-30. Epub 2008 Apr 6.

Moreover, galectin-1 increased glucose transporter-1 mRNA and protein expression levels, which were inhibited by a disruption in transcription by actinomycin D and translation by the cycloheximide.
4(0,0,0,4) Details
16895520 Carmosino M, Procino G, Tamma G, Mannucci R, Svelto M, Valenti G: Trafficking and phosphorylation dynamics of AQP4 in histamine-treated human gastric cells. Biol Cell. 2007 Jan;99(1):25-36.


Using an endo-exocytosis assay we showed that, after histamine washed out, internalized AQP4 recycled back to the cell surface, even in cells in which de novo protein synthesis was inhibited by cycloheximide.
0(0,0,0,0) Details
16464174 Malakooti J, Sandoval R, Amin MR, Clark J, Dudeja PK, Ramaswamy K: Transcriptional stimulation of the human NHE3 promoter activity by PMA: PKC independence and involvement of the transcription factor EGR-1. Biochem J. 2006 Jun 1;396(2):327-36.


Pretreatment with actinomycin D or cycloheximide blocked the up-regulation of the NHE3 mRNA by PMA, indicating that the increased level of NHE3 mRNA expression is regulated by transcriptional activation and is dependent on de novo protein synthesis. 5'-Deletion of the promoter region and transfection analysis in C2BBe1 cells revealed that the PMA effect is mediated through a GC-rich DNA region between nt -88 and -69.
0(0,0,0,0) Details
15569273 Luo G, Xu CB, Cao YX, Edvinsson L: Transcriptional up-regulation in expression of 5-hydroxytryptamine2A and transcriptional down-regulation of angiotensin II type 1 receptors during organ culture of rat mesenteric artery. Basic Clin Pharmacol Toxicol. 2004 Dec;95(6):280-7.


The purpose of this study was to investigate in rat mesenteric artery if there is up-regulation of 5-hydroxytryptamine (5-HT) receptors and angiotensin II receptors and the potential role of protein kinase C activation in the smooth muscle cells during organ culture.
2(0,0,0,2) Details
17156130 Kalfon L, Youdim MB, Mandel SA: Green tea polyphenol (-) -epigallocatechin-3-gallate promotes the rapid protein kinase C- and proteasome-mediated degradation of Bad: implications for neuroprotection. J Neurochem. 2007 Feb;100(4):992-1002. Epub 2006 Nov 29.

Co-treatment with EGCG and the protein synthesis inhibitor cycloheximide prominently shortened Bad half-life, with as little as 30% of the Bad protein content remaining after 2 h, suggesting an effect of EGCG on Bad protein degradation.
2(0,0,0,2) Details
17596302 Ye J, Gradoville L, Daigle D, Miller G: De novo protein synthesis is required for lytic cycle reactivation of Epstein-Barr virus, but not Kaposi's sarcoma-associated herpesvirus, in response to histone deacetylase inhibitors and protein kinase C agonists. J Virol. 2007 Sep;81(17):9279-91. Epub 2007 Jun 27.


Using Northern blotting and quantitative reverse transcriptase PCR, we measured the kinetics of expression of the lytic cycle activator genes and determined whether abundance of mRNAs encoding these genes from either virus was reduced by treatment with cycloheximide (CHX), an inhibitor of protein synthesis.
0(0,0,0,0) 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.
0(0,0,0,0) Details
15936242 Lee YS, Paek KS, Kang ES, Jang HS, Kim HJ, Kang YJ, Kim JH, Lee HT, Lee JH, Chang KC, Nishinaka T, Seo HG: Involvement of nuclear factor kappaB in up-regulation of aldose reductase gene expression by 12-O-tetradecanoylphorbol-13-acetate in HeLa cells. Int J Biochem Cell Biol. 2005 Nov;37(11):2297-309.


Inhibitors of protein kinase C, bisindolylmaleimide I and calphostin C, as well as inhibitors of tyrosine kinase, genistein and tyrphostin A23, significantly attenuated 12-O-tetradecanoylphorbol-13-acetate-induced increase in aldose reductase mRNA.
2(0,0,0,2) Details
19920324 Ji L, Chauhan A, Chauhan V: Upregulation of Cytoplasmic Gelsolin, an Amyloid-beta-Binding Protein, Under Oxidative Stress Conditions: Involvement of Protein Kinase C. J Alzheimers Dis. 2009 Nov 17.

Pretreatment of cells with cycloheximide (an inhibitor of protein synthesis) resulted in significant inhibition of H _2 O _2 -induced c-gelsolin expression, suggesting the possible de novo synthesis of c-gelsolin in cells.
2(0,0,0,2) Details
20157239 Ji L, Chauhan A, Chauhan V: Upregulation of cytoplasmic gelsolin, an amyloid-beta-binding protein, under oxidative stress conditions: involvement of protein kinase C. J Alzheimers Dis. 2010 Jan;19(3):829-38.

Pretreatment of cells with cycloheximide (an inhibitor of protein synthesis) resulted in significant inhibition of H (2) O (2) induced c-gelsolin expression, suggesting the possible de novo synthesis of c-gelsolin in cells.
2(0,0,0,2) Details
19179479 Armstrong SP, Caunt CJ, McArdle CA: Gonadotropin-releasing hormone and protein kinase C signaling to ERK: spatiotemporal regulation of ERK by docking domains and dual-specificity phosphatases. Mol Endocrinol. 2009 Apr;23(4):510-9. Epub 2009 Jan 29.

Cycloheximide caused more sustained effects of GnRH and phorbol ester on ppERK, suggesting termination by nuclear-inducible DUSPs.
2(0,0,0,2) Details
16926447 Lanaspa MA, Giral H, Breusegem SY, Halaihel N, Baile G, Catalan J, Carrodeguas JA, Barry NP, Levi M, Sorribas V: Interaction of MAP17 with NHERF3/4 induces translocation of the renal Na/Pi IIa transporter to the trans-Golgi. Am J Physiol Renal Physiol. 2007 Jan;292(1):F230-42. Epub 2006 Aug 22.


Inhibition of protein kinase C (PKC) prevented expression of the three proteins in the TGN.
1(0,0,0,1) Details
19693770 Tsai JH, Hwang JM, Ying TH, Shyu JC, Tsai CC, Hsieh YS, Wang YW, Liu JY, Kao SH: The activation of matrix metalloproteinase-2 induced by protein kinase C alpha in decidualization. J Cell Biochem. 2009 Oct 15;108(3):547-54.

This study investigated the protein kinase C (PKC) and matrix metalloproteinase-2 (MMP-2) in the development of deciduomata in pseudo-pregnant and pregnant rats.
Moreover, this response was inhibited by the PKC inhibitor H7, the PKC alpha specific inhibitor Go-6976 and the translation inhibitor cycloheximide, but not by the transcription inhibitor actinomycin D or the replication inhibitor mitomycin C.
1(0,0,0,1) Details
18404734 Tattersall AL, Wilkins RJ: Modulation of Na+-H+ exchange isoforms NHE1 and NHE3 by insulin-like growth factor-1 in isolated bovine articular chondrocytes. J Orthop Res. 2008 Nov;26(11):1428-33.

NHE3 activity was not detected in IGF-1-treated cells that had been incubated with the protein synthesis inhibitor cycloheximide, although NHE1 activity was unaffected.
For raised hydrostatic pressure, a decrease in NHE1 activity was responsible, and was prevented by the protein kinase C inhibitor chelerythrine.
1(0,0,0,1) Details
16075364 Phelps E, Bezouglaia O, Tetradis S, Nervina JM: Parathyroid hormone induces receptor activity modifying protein-3 (RAMP3) expression primarily via 3',5'-cyclic adenosine monophosphate signaling in osteoblasts. Calcif Tissue Int. 2005 Aug;77(2):96-103. Epub 2005 Aug 11.

PTH induces osteoblastic gene expression through PTHR1, a heptahelical receptor that triggers cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA), protein kinase C (PKC), and calcium signaling.
Protein synthesis inhibition with 3 microg/mL cycloheximide did not affect PTH-induced RAMP3 mRNA levels.
1(0,0,0,1) 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.

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.
Nicotine increased IRS-1 and IRS-2 mRNA levels by approximately 57 and approximately 50%, and this was prevented by conventional protein kinase C (cPKC) inhibitor Go6976, or ERK kinase inhibitors PD98059 and U0126.
1(0,0,0,1) 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.

The initial block in GJIC has been attributed to protein kinase C (PKC) mediated phosphorylation of connexin gap junction proteins, including connexin43 (Cx43).
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.
1(0,0,0,1) Details
15928807 Kang ES, Kim HJ, Paek KS, Jang HS, Chang KC, Lee JH, Nishinaka T, Yabe-Nishimura C, Seo HG: Phorbol ester up-regulates aldose reductase expression in A549 cells: a potential role for aldose reductase in cell cycle modulation. Cell Mol Life Sci. 2005 May;62(10):1146-55.


The TPA-induced increase in mRNA level and promoter activity of the AR gene was significantly attenuated in the presence of an inhibitor of protein kinase C, tyrosine kinase, or nuclear factor kappaB (NF-kappaB).
1(0,0,0,1) 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.
1(0,0,0,1) Details
17438304 Sonalker PA, Jackson EK: Norepinephrine, via beta-adrenoceptors, regulates bumetanide-sensitive cotransporter type 1 expression in thick ascending limb cells. Hypertension. 2007 Jun;49(6):1351-7. Epub 2007 Apr 16.

Treatment with norepinephrine, either alone or in the presence of actinomycin D or cycloheximide, had no effect on cotransporter mRNA levels.
To further elucidate the mechanism, thick ascending limb cells were treated with norepinephrine in the presence of phentolamine (alpha-adrenoceptor blocker), propranolol (beta-adrenoceptor blocker), SQ22536 (adenylyl cyclase inhibitor), PD098059 (mitogen-activated protein kinase pathway inhibitor), H-89 (protein kinase A inhibitor), or staurosporine (protein kinase C inhibitor).
1(0,0,0,1) Details
16330215 Fujimoto S, Katsuki H, Kume T, Akaike A: Thrombin-induced delayed injury involves multiple and distinct signaling pathways in the cerebral cortex and the striatum in organotypic slice cultures. Neurobiol Dis. 2006 Apr;22(1):130-42. Epub 2005 Dec 5.

These effects were prevented by cycloheximide and actinomycin D but not by a caspase-3 inhibitor.
In addition, inhibition of extracelluar signal-regulated kinase (ERK), Src tyrosine kinase and protein kinase C prevented both neuronal injury in the cortex and shrinkage of the striatum, whereas inhibition of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase prevented shrinkage of the striatum only.
1(0,0,0,1) Details
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.


Protein kinase C (PKC) is implicated in the nongenomic effects of aldosterone.
1(0,0,0,1) Details
18719002 Pritchard DM, Berry D, Przemeck SM, Campbell F, Edwards SW, Varro A: Gastrin increases mcl-1 expression in type I gastric carcinoid tumors and a gastric epithelial cell line that expresses the CCK-2 receptor. Am J Physiol Gastrointest Liver Physiol. 2008 Oct;295(4):G798-805. Epub 2008 Aug 21.

Gastrin therefore signals via the CCK-2 receptor, protein kinase C, and MAP kinase to induce expression of antiapoptotic mcl-1 in AGS-G (R) cells, and mcl-1 expression is also increased in human hypergastrinemia-associated type I gastric carcinoid tumors.
Gastrin-induced mcl-1 expression was inhibited by the transcription inhibitor actinomycin D and by the protein synthesis inhibitor cycloheximide.
1(0,0,0,1) Details
19223651 Dominguez B, Felix R, Monjaraz E: Upregulation of voltage-gated Na+ channels by long-term activation of the ghrelin-growth hormone secretagogue receptor in clonal GC somatotropes. Am J Physiol Endocrinol Metab. 2009 May;296(5):E1148-56. Epub 2009 Feb 17.


Conversely, treatment with a cAMP analog or a protein kinase C activator enhanced both basal and GHS-induced secretion of GH measured by enzyme-linked immunoassay, suggesting that GHRP-6 acting through the ghrelin receptor and different signaling pathways enhances Na (+) channel membrane expression, which favors hormone release from GC somatotropes.
1(0,0,0,1) Details
18094537 Ikewaki N, Tamauchi H, Inoko H: Decrease in CD93 (C1qRp) expression in a human monocyte-like cell line (U937) treated with various apoptosis-inducing chemical substances. Microbiol Immunol. 2007;51(12):1189-200.


We previously reported that a protein kinase C activator (PKC), phorbol myristate acetate (PMA), effectively up-regulated CD93 expression on several cultured cell lines and that its regulation was mainly controlled by a PKC delta-isoenzyme.
1(0,0,0,1) Details
18651560 Yuan G, Nanduri J, Khan S, Semenza GL, Prabhakar NR: Induction of HIF-1alpha expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J Cell Physiol. 2008 Dec;217(3):674-85.

Rapamycin or cycloheximide, blocked increased HIF-1alpha levels during re-oxygenation indicating that mTOR-dependent protein synthesis is required for the persistent elevation of HIF-1alpha levels during re-oxygenation.
We further demonstrate that ROS-dependent Ca (2+) signaling pathways involving phospholipase Cgamma (PLCgamma) and protein kinase C activation are required for IH-evoked HIF-1alpha accumulation.
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20042606 Cardoso LE, Little PJ, Ballinger ML, Chan CK, Braun KR, Potter-Perigo S, Bornfeldt KE, Kinsella MG, Wight TN: Platelet-derived growth factor differentially regulates the expression and post-translational modification of versican by arterial smooth muscle cells through distinct protein kinase C and extracellular signal-regulated kinase pathways. J Biol Chem. 2010 Mar 5;285(10):6987-95. Epub 2009 Dec 30.

Interestingly, blocking protein synthesis in the presence of cycloheximide abolished the PDGF effect, but not in the presence of xyloside, indicating that GAG synthesis that results from PKC activation is independent from de novo protein synthesis.
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20207835 Gonzalez-Montelongo MC, Marin R, Gomez T, Marrero-Alonso J, Diaz M: Androgens Induce Nongenomic Stimulation of Colonic Contractile Activity through Induction of Calcium Sensitization and Phosphorylation of LC20 and CPI-17. Mol Endocrinol. 2010 Mar 5.

The results using flutamide, finasteride, cycloheximide, and actinomycin D indicate that androgen-induced potentiation is dependent on androgen receptors, requires reduction of testosterone to DHT, and occurs independently of transcriptional and translational events.
Paralleling these findings, inhibition of Rho-associated Rho kinase (ROK) and/or protein kinase C (PKC) with, respectively, Y27632 and chelerythrine, prevented LC20 phosphorylation and abolished calcium sensitization.
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15547951 Chiou GY, Fong JC: Synergistic effect of prostaglandin F2alpha and cyclic AMP on glucose transport in 3T3-L1 adipocytes. J Cell Biochem. 2005 Feb 15;94(3):627-34.

The synergistic effect of these two agents was suppressed in the presence of cycloheximide and actinomycin D.
The synergistic action of PGF2alpha with 8-bromo cAMP to enhance glucose transport was inhibited by GF109203X, a selective protein kinase C (PKC) inhibitor.
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18303026 Tatematsu K, Yoshimoto N, Okajima T, Tanizawa K, Kuroda S: Identification of ubiquitin ligase activity of RBCK1 and its inhibition by splice variant RBCK2 and protein kinase Cbeta. J Biol Chem. 2008 Apr 25;283(17):11575-85. Epub 2008 Feb 25.


We previously identified a RING-IBR protein, RBCK1, as a protein kinase C (PKC) beta- and zeta-interacting protein, and its splice variant, RBCK2, lacking the C-terminal half including the RING-IBR domain.
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15519494 Yoshida M, Niwa M, Ishisaki A, Hirade K, Ito H, Shimizu K, Kato K, Kozawa O: Methotrexate enhances prostaglandin D2-stimulated heat shock protein 27 induction in osteoblasts. Prostaglandins Leukot Essent Fatty Acids. 2004 Dec;71(6):351-62.


We previously showed that PGD2 stimulates the induction of heat shock protein 27 (HSP27) via protein kinase C (PKC)-dependent p38 mitogen-activated protein (MAP) kinase and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells.
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16293985 Sarker KP, Biswas KK, Yamaji K, Yamakuchi M, Hashiguchi T, Lee KY, Maruyama I: Inhibition of thrombin-induced vascular endothelial growth factor production in human neuroblastoma (NB-1) cells by argatroban. Pathophysiol Haemost Thromb. 2005;34(1):41-7.

In these cells, we further show that thrombin-induced VEGF secretion was blocked by cycloheximide and actinomycin D, indicating that de novo protein synthesis is essential for this process.
Reduced thrombin-induced VEGF secretion upon treatment with LY294002, calphostin C, or BAPTA, further suggests that the process is dependent on phosphatidyl-inositol-3-kinase, protein kinase C, and calcium.
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15837527 Tenhunen O, Szokodi I, Ruskoaho H: Posttranscriptional activation of BNP gene expression in response to increased left ventricular wall stress: role of calcineurin and PKC. Regul Pept. 2005 Jun 30;128(3):187-96.

In contrast, the protein synthesis inhibitor cycloheximide increased baseline BNP mRNA levels and abolished the load-induced activation of gene expression.
Furthermore, we studied the effects of protein kinase C (PKC), calcineurin and protein phosphatase 2A (PP2A) inhibition to characterize the role of intracellular pathways in the stretch-induced gene expression in the left ventricle.
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