Protein Information

Name protein kinase A (protein family or complex)
Synonyms Protein kinase A; cAMP dependent protein kinase; cAMP dependent protein kinases

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
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.
32(0,1,1,2) Details
19540219 Fu Z, Liu D: Long-term exposure to genistein improves insulin secretory function of pancreatic beta-cells. Eur J Pharmacol. 2009 Aug 15;616(1-3):321-7. Epub 2009 Jun 18.

The enhanced insulin secretion by genistein was associated with elevated intracellular Ca (2+) concentration and dependent on protein kinase A and new protein synthesis as this effect was completely blocked by N-[2-(p-Bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide or cycloheximide.
31(0,1,1,1) 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).
3(0,0,0,3) 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).
2(0,0,0,2) Details
18425542 Sosa OA, de Nadra MC, Farias ME: Modification by glucose of the flocculent phenotype of a Kloeckera apiculata wine strain. J Ind Microbiol Biotechnol. 2008 Aug;35(8):851-7. Epub 2008 Apr 19.

To elucidate the mechanism involved in flocculation induction, cycloheximide was injected into the cultures 120 min before the glucose pulse. 2,4-Dinitrophenol or cAMP was added to the media instead, or simultaneously with glucose, while a protein kinase A (PKA) inhibitor was added 30 min before the glucose pulse.
31(0,1,1,1) Details
17122036 Armstrong GA, Shoemaker KL, Money TG, Robertson RM: Octopamine mediates thermal preconditioning of the locust ventilatory central pattern generator via a cAMP/protein kinase A signaling pathway. J Neurosci. 2006 Nov 22;26(47):12118-26.

Octopamine-mediated thermoprotection was also abolished with neuropil injections of cycloheximide or actinomycin D, indicating a requirement for transcription and translation.
2(0,0,0,2) Details
15604115 Yeagley D, Quinn PG: 3',5'-cyclic adenosine monophosphate response element-binding protein and CCAAT enhancer-binding protein are dispensable for insulin inhibition of phosphoenolpyruvate carboxykinase transcription and for its synergistic induction by protein kinase A and glucocorticoids. Mol Endocrinol. 2005 Apr;19(4):913-24. Epub 2004 Dec 16.

Cycloheximide did not block insulin inhibition, indicating that alternate translation of C/EBPbeta is not required.
2(0,0,0,2) Details
17045344 Mukhopadhyay S, Das S, Williams EA, Moore D, Jones JD, Zahm DS, Ndengele MM, Lechner AJ, Howlett AC: Lipopolysaccharide and cyclic AMP regulation of CB (2) cannabinoid receptor levels in rat brain and mouse RAW 264.7 macrophages. J Neuroimmunol. 2006 Dec;181(1-2):82-92. Epub 2006 Oct 10.


LPS increased immunodetectable CB (2) receptors in cultured RAW 264.7 macrophages, and this was partially attenuated by cyclohexamide or the protein kinase A and C inhibitors H8 and bis-indolylmaleimide.
2(0,0,0,2) Details
18647593 Ozaki Y, Kato T, Kitagawa M, Fujita H, Kitagawa S: Calpain inhibition delays neutrophil apoptosis via cyclic AMP-independent activation of protein kinase A and protein kinase A-mediated stabilization of Mcl-1 and X-linked inhibitor of apoptosis (XIAP). Arch Biochem Biophys. 2008 Sep 15;477(2):227-31. Epub 2008 Jul 11.

Calpain inhibitors (PD150606 and N-acetyl-Leu-Leu-Nle-CHO) prevented spontaneous neutrophil apoptosis and degradation of Mcl-1 and XIAP, and the effects of calpain inhibitors on neutrophils were resistant to cycloheximide.
2(0,0,0,2) Details
16197501 Ghosh M, Gharami K, Paul S, Das S: Thyroid hormone-induced morphological differentiation and maturation of astrocytes involves activation of protein kinase A and ERK signalling pathway. Eur J Neurosci. 2005 Oct;22(7):1609-17.

2(0,0,0,2) 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.
Unresponsiveness to hyperosmotic shock represented inhibition of NHE3 activity, and was prevented using the protein kinase A inhibitor KT5720.
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
17064391 Sosroseno W, Musa M, Ravichandran M, Fikri Ibrahim M, Bird PS, Seymour GJ: The role of cyclic-AMP on arginase activity by a murine macrophage cell line (RAW264.7) stimulated with lipopolysaccharide from Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol. 2006 Dec;21(6):347-52.

The effects of SQ22536 (an adenylyl cyclase inhibitor), ODQ (a guanylyl cyclase inhibitor), dibutyryl cAMP (a cAMP analog), 8-bromo cyclic guanosine monophosphate (a cGMP analog), forskolin (an adenylyl cylase activator), and cycloheximide (a protein synthesis inhibitor) on arginase activity in A. actinomycetemcomitans LPS-stimulated RAW264.7 cells were also determined.
Arginase activity was assessed in LPS-stimulated cells in the presence of 3-isobutyl-1-methylxanthine (IBMX), siguazodan and rolipram [phosphodiesterase (PDE) inhibitors] as well as KT5720 [a protein kinase A (PKA) inhibitor].
1(0,0,0,1) Details
16299053 Busch CJ, Liu H, Graveline AR, Bloch KD: Nitric oxide induces phosphodiesterase 4B expression in rat pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2006 Apr;290(4):L747-L753. Epub 2005 Nov 18.

The soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4] oxadiazolo [4,3,-a] quinoxalin-1-one, and the cAMP-dependent protein kinase inhibitor, H89, prevented induction of PDE4B gene expression by GSNO, but the protein kinase G (PKG) inhibitors, Rp-8-pCPT-cGMPs and KT-5823, did not.
The GSNO-induced increase in PDE4B mRNA levels was blocked by actinomycin D but augmented by cycloheximide.
1(0,0,0,1) Details
19711044 Yum J, Jeong HM, Kim S, Seo JW, Han Y, Lee KY, Yeo CY: PKA-mediated stabilization of FoxH1 negatively regulates ERalpha activity. Mol Cells. 2009 Jul;28(1):67-71. Epub 2009 Jul 8.


ERalpha can also be activated in a ligand-independent manner by many signaling pathways, including protein kinase A (PKA) signaling.
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
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
19162058 Roy B, Rai U: Genomic and non-genomic effect of cortisol on phagocytosis in freshwater teleost Channa punctatus: an in vitro study. Steroids. 2009 Apr-May;74(4-5):449-55. Epub 2008 Dec 31.


Using inhibitors for adenylate cyclase/protein kinase A (PKA) and estimating intracellular cAMP, adenylate cyclase-PKA pathway was seen involved in mediating the rapid non-genomic action of cortisol in phagocytes of C. punctatus.
1(0,0,0,1) Details
19880179 Ni XT, Duan T, Yang Z, Guo CM, Li JN, Sun K: Role of human chorionic gonadotropin in maintaining 11beta-hydroxysteroid dehydrogenase type 2 expression in human placental syncytiotrophoblasts. Placenta. 2009 Dec;30(12):1023-8. Epub 2009 Oct 31.


By using cultured human placental syncytiotrophoblasts, we demonstrated that inhibition of protein kinase A with H89 attenuated 11beta-HSD2 expression in the syncytiotrophoblasts, suggesting endogenous factors from the syncytiotrophoblasts using this pathway to maintain 11beta-HSD2 expression in the syncytiotrophoblasts.
1(0,0,0,1) Details
19398497 Kang JH, Chang SY, Jang HJ, Kim DB, Ryu GR, Ko SH, Jeong IK, Jo YH, Kim MJ: Exendin-4 inhibits interleukin-1beta-induced iNOS expression at the protein level, but not at the transcriptional and posttranscriptional levels, in RINm5F beta-cells. J Endocrinol. 2009 Jul;202(1):65-75. Epub 2009 Apr 27.

Meanwhile, forskolin significantly inhibited IL-1beta-induced iNOS protein, which was reversed by H-89, a protein kinase A (PKA) inhibitor.
Additionally, the cycloheximide chase study demonstrated that EX-4 significantly accelerated iNOS protein degradation.
1(0,0,0,1) Details
16705092 Kim JS, Kim JG, Moon MY, Jeon CY, Won HY, Kim HJ, Jeon YJ, Seo JY, Kim JI, Kim J, Lee JY, Kim PH, Park JB: Transforming growth factor-beta1 regulates macrophage migration via RhoA. Blood. 2006 Sep 15;108(6):1821-9. Epub 2006 May 16.

Cycloheximide, actinomycin D, and antibodies against MIP-1alpha and monocyte chemoattractant protein-1 (MCP-1) abolished the stimulation of cell migration by TGF-beta1.
First, TGF-beta1 phosphorylated RhoA via protein kinase A, leading to inactivation of RhoA.
1(0,0,0,1) Details
15727843 Huang NK, Cheng JJ, Lai WL, Lu MK: Antrodia camphorata prevents rat pheochromocytoma cells from serum deprivation-induced apoptosis. FEMS Microbiol Lett. 2005 Mar 1;244(1):213-9.


Inhibitors of both a serine/threonine kinase and a specific protein kinase A (PKA) inhibited the protective effect of A. camphorata, indicating that A. camphorata prevents serum-deprived PC12 cell apoptosis through a PKA-dependent mechanism.
1(0,0,0,1) Details
17446180 Chik CL, Wloka MT, Price DM, Ho AK: The role of repressor proteins in the adrenergic induction of type II iodothyronine deiodinase in rat pinealocytes. Endocrinology. 2007 Jul;148(7):3523-31. Epub 2007 Apr 19.

Both beta- and alpha1-adrenergic receptors contributed to the NE induction of Dio2 expression through a cAMP/protein kinase A mechanism.
In contrast, inhibition of protein synthesis by cycloheximide enhanced the NE induction of Dio2 expression, suggesting the involvement of a repressor protein.
1(0,0,0,1) Details
19967152 Ishii H, Kojima Y, Masuda Y, Takada K, Sugimoto K, Ikeda T: Expression of thrombin-activatable fibrinolysis inhibitor (TAFI) is up-regulated by increase in intracellular cyclic AMP levels in cultured HepG2 cells. Thromb Haemost. 2009 Dec;102(6):1204-11.


The elevated TAFI expression was abolished by pretreatment of the cells with KT5720, a protein kinase A (PKA) inhibitor.
1(0,0,0,1) Details
15545276 Park JI, Collinson EJ, Grant CM, Dawes IW: Rom2p, the Rho1 GTP/GDP exchange factor of Saccharomyces cerevisiae, can mediate stress responses via the Ras-cAMP pathway. J Biol Chem. 2005 Jan 28;280(4):2529-35. Epub 2004 Nov 15.

Subsequent analysis of strains with a rom2 deletion showed that Rom2p is essential for resistance to a variety of stresses caused by freeze-thawing, oxidants, cycloheximide, NaCl, or cobalt ions.
Stress sensitivity and the growth defect caused by the rom2 deletion could be suppressed by depleting Ras or protein kinase A (PKA) activity or by overexpressing the high affinity cAMP phosphodiesterase Pde2p.
1(0,0,0,1) Details
19470703 Kanyo R, Price DM, Chik CL, Ho AK: Salt-inducible kinase 1 in the rat pinealocyte: adrenergic regulation and role in arylalkylamine N-acetyltransferase gene transcription. Endocrinology. 2009 Sep;150(9):4221-30. Epub 2009 May 21.


Together, our results indicate that the adrenergic induction of Sik1 in the rat pineal gland is primarily through the beta-adrenergic receptor --> protein kinase A pathway.
1(0,0,0,1) Details
17218408 Sasseville M, Cote N, Vigneault C, Guillemette C, Richard FJ: 3'5'-cyclic adenosine monophosphate-dependent up-regulation of phosphodiesterase type 3A in porcine cumulus cells. Endocrinology. 2007 Apr;148(4):1858-67. Epub 2007 Jan 11.

PMSG-dependent Pde3 activation was inhibited by the protein kinase A-specific inhibitor H89.
The cilostamide-sensitive increase in PDE activity was inhibited by a protein synthesis inhibitor, cycloheximide.
1(0,0,0,1) 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.

RESULTS: We found that the induction of fgf-2 by MS is dependent on both protein kinase A (PKA) and ERK pathways.
Pretreatment of MC3T3-E1 cells with cycloheximide showed that the induction of fgf-2 did not require new protein synthesis.
1(0,0,0,1) Details
18493739 Wang Q, Heimberg H, Pipeleers D, Ling Z: Glibenclamide activates translation in rat pancreatic beta cells through calcium-dependent mTOR, PKA and MEK signalling pathways. Diabetologia. 2008 Jul;51(7):1202-12. Epub 2008 May 21.

Since it was blocked by the translation inhibitor cycloheximide, we examined whether sustained exposure to glibenclamide activates translational factors by calcium-dependent signalling pathways.
This activation of translational factors and the associated elevation of insulin synthesis were completely blocked by the calcium channel blocker verapamil and partially blocked by the mammalian target of rapamycin (mTOR) inhibitor rapamycin, the protein kinase A (PKA) inhibitor Rp-8-Br-cAMPs and the mitogen-activated protein kinase/ extracellular signal-regulated kinase kinase (MEK) inhibitor U0126; a combination of inhibitors exhibited additive effects.
1(0,0,0,1) 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
18442936 Lai YT, Fan HY, Cherng CG, Chiang CY, Kao GS, Yu L: Activation of amygdaloid PKC pathway is necessary for conditioned cues-provoked cocaine memory performance. Neurobiol Learn Mem. 2008 Jul;90(1):164-70. Epub 2008 Apr 28.


Likewise, a similar blockade of cues-provoked cocaine CPP performance was achieved by infusion of anisomycin and cycloheximide into the basolateral nuclei of amygdala before the test.
0(0,0,0,0) Details
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.

Addition of GGPP abolished simvastatin-induced stimulation of cAMP accumulation and protein kinase A (PKA) activity.
Simvastatin inhibition of leptin gene transcription was not abrogated by pre-treatment with cycloheximide, an inhibitor of protein synthesis.
1(0,0,0,1) Details