PROTEIN KINASE A (PKA) SIGNALING PATHWAY (PW:0000543)

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Description

Protein kinase A (PKA) signaling is a widely used intracellular pathway and the major route for channeling the second messenger cAMP signal. Ligand activated G-protein coupled receptors that transduce the signal via the Gs alpha subunit of the heterotrimeric G protein lead to activation of the adenylyl cyclase enzymes (AC) that catalyze the formation of cAMP from ATP. GTP-bound Gs binds to AC and increases the affinity between the C1 and C2 cytoplasmic domains whose interface constitutes t

Pathway Diagram:

Elsevier Inc. GPCRs upstream PKA Gnas ---- GPCRs upstream PKA Gnas AC members G protein mediated signaling pathway via Galphas family Pka complex ---> cytoskeleton dynamics ATP ---> cAMP nuclear dynamics cytoskeleton dynamics Pka complex Gnas --+> AC members cAMP --+> Pka complex regulation of ion channels cardiovascular function Pka complex ---> gene expression Akaps Pdes cAMP ATP metabolism exocytosis gene expression Pka complex ---> nuclear dynamics Pdes ---| cAMP regulation of neuroreceptors Pka complex ---> metabolism Pka complex ---> regulation of neuroreceptors Pka complex ---> cardiovascular function Pka complex ---> regulation of ion channels Pka complex ---> exocytosis
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Genes in Pathway:

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protein kinase A (PKA) signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Adcy1 adenylate cyclase 1 JBrowse link 14 87,311,970 87,429,880 RGD:2312469
G Adcy10 adenylate cyclase 10 JBrowse link 13 83,701,952 83,787,010 RGD:2312469
G Adcy2 adenylate cyclase 2 JBrowse link 1 37,043,071 37,698,390 RGD:2312469
G Adcy3 adenylate cyclase 3 JBrowse link 6 28,570,941 28,648,848 RGD:2312469
G Adcy4 adenylate cyclase 4 JBrowse link 15 34,453,917 34,469,779 RGD:2312469
G Adcy5 adenylate cyclase 5 JBrowse link 11 68,695,839 68,842,452 RGD:2312469
G Adcy6 adenylate cyclase 6 JBrowse link 7 140,270,678 140,291,722 RGD:2312469
RGD:2313211
G Adcy7 adenylate cyclase 7 JBrowse link 19 19,702,307 19,762,973 RGD:2312469
G Adcy8 adenylate cyclase 8 JBrowse link 7 105,353,883 105,593,372 RGD:2312469
G Adcy9 adenylate cyclase 9 JBrowse link 10 11,392,698 11,515,406 RGD:2312469
G Akap1 A-kinase anchoring protein 1 JBrowse link 10 76,151,013 76,183,987 RGD:2312475
RGD:2312477
G Akap10 A-kinase anchoring protein 10 JBrowse link 10 48,150,902 48,210,074 RGD:2312475
RGD:2312477
G Akap11 A-kinase anchoring protein 11 JBrowse link 15 60,722,138 60,766,673 RGD:2312475
RGD:2312637
RGD:2312477
G Akap12 A-kinase anchoring protein 12 JBrowse link 1 40,816,130 40,906,582 RGD:2312475
RGD:2312477
G Akap13 A-kinase anchoring protein 13 JBrowse link 1 137,089,558 137,315,272 RGD:2312475
RGD:2312477
G Akap14 A-kinase anchoring protein 14 JBrowse link X 123,773,430 123,788,898 RGD:2312475
RGD:2312477
G Akap2 A-kinase anchoring protein 2 JBrowse link 5 74,874,245 74,985,789 RGD:2312475
RGD:2312477
G Akap3 A-kinase anchoring protein 3 JBrowse link 4 159,399,686 159,425,512 RGD:2312475
RGD:2312477
G Akap4 A-kinase anchoring protein 4 JBrowse link X 16,296,027 16,306,078 RGD:2312475
RGD:2312477
G Akap5 A-kinase anchoring protein 5 JBrowse link 6 99,356,509 99,361,909 RGD:2312475
RGD:2312477
G Akap6 A-kinase anchoring protein 6 JBrowse link 6 73,553,111 73,991,992 RGD:2312475
RGD:68716
RGD:2312477
G Akap7 A-kinase anchoring protein 7 JBrowse link 1 21,129,213 21,263,850 RGD:2312475
RGD:2312630
RGD:2312477
G Akap8 A-kinase anchoring protein 8 JBrowse link 7 14,323,298 14,339,953 RGD:2312475
RGD:2312477
G Akap9 A-kinase anchoring protein 9 JBrowse link 4 27,195,346 27,331,582 RGD:2312475
RGD:2312477
G Crhr2 corticotropin releasing hormone receptor 2 JBrowse link 4 85,286,371 85,329,374 RGD:5131271
G Ezr ezrin JBrowse link 1 47,287,872 47,331,412 RGD:2312475
G Pde10a phosphodiesterase 10A JBrowse link 1 52,360,296 52,544,448 RGD:2312479
G Pde11a phosphodiesterase 11A JBrowse link 3 62,818,502 63,211,843 RGD:2312479
G Pde1a phosphodiesterase 1A JBrowse link 3 66,803,247 67,263,658 RGD:2312479
G Pde1b phosphodiesterase 1B JBrowse link 7 145,117,951 145,147,711 RGD:2312479
G Pde1c phosphodiesterase 1C JBrowse link 4 86,359,762 86,925,044 RGD:2312479
G Pde2a phosphodiesterase 2A JBrowse link 1 166,534,643 166,626,158 RGD:2312479
G Pde3a phosphodiesterase 3A JBrowse link 4 175,431,904 175,703,844 RGD:2312479
G Pde3b phosphodiesterase 3B JBrowse link 1 183,892,841 184,078,071 RGD:2312479
G Pde4a phosphodiesterase 4A JBrowse link 8 22,189,533 22,234,036 RGD:2312479
G Pde4b phosphodiesterase 4B JBrowse link 5 121,759,236 122,136,814 RGD:2312479
G Pde4c phosphodiesterase 4C JBrowse link 16 20,442,305 20,466,386 RGD:2312479
G Pde4d phosphodiesterase 4D JBrowse link 2 40,219,999 41,468,551 RGD:2312479
RGD:68716
G Pde7a phosphodiesterase 7A JBrowse link 2 104,042,124 104,134,101 RGD:2312479
G Pde7b phosphodiesterase 7B JBrowse link 1 15,889,845 16,203,909 RGD:2312479
G Pde8a phosphodiesterase 8A JBrowse link 1 143,036,083 143,160,395 RGD:2312479
G Pde8b phosphodiesterase 8B JBrowse link 2 24,718,548 24,955,533 RGD:2312479
G Prkaca protein kinase cAMP-activated catalytic subunit alpha JBrowse link 19 25,095,089 25,118,869 RGD:2312475
G Prkacb protein kinase cAMP-activated catalytic subunit beta JBrowse link 2 252,602,197 252,691,886 RGD:2312475
G Prkar1a protein kinase cAMP-dependent type 1 regulatory subunit alpha JBrowse link 10 97,940,705 97,959,199 RGD:2312475
G Prkar1b protein kinase cAMP-dependent type 1 regulatory subunit beta JBrowse link 12 17,614,536 17,713,567 RGD:2312475
G Prkar2a protein kinase cAMP-dependent type 2 regulatory subunit alpha JBrowse link 8 117,486,085 117,548,768 RGD:2312475
G Prkar2b protein kinase cAMP-dependent type 2 regulatory subunit beta JBrowse link 6 51,265,509 51,356,383 RGD:2312475

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Functional ClassAkapsA Kinase Anchoring Protein family members
Functional ClassACadenylyl (adenylate) cyclase family members
Functional ClassPdesphosphopdiesterase family members
ComplexPka complexthe regulatory and catalytic subunits of serine/threonine protein kinase A (PKA) complex

Pathway Gene Annotations

Disease Annotations Associated with Genes in the protein kinase A (PKA) signaling pathway
Disease TermsGene Symbols
Abnormalities, MultipleAdcy5
AcrodysostosisPde4d , Prkar1a
Acrodysostosis 1, with or without Hormone ResistancePrkar1a
Acrodysostosis 2, with or without Hormone ResistancePde4d
Adrenal Cortex NeoplasmsPrkar1a
Adrenal Gland NeoplasmsPrkaca
Adrenal Hyperplasia, CongenitalPde8b , Prkar1a
AlcoholismPde4b
Alzheimer DiseaseAkap5 , Pde2a
Amelogenesis Imperfecta NephrocalcinosisPrkar1a
AMELOGENESIS IMPERFECTA, TYPE IGPrkar1a
Amphetamine-Related DisordersPde4b , Pde4d
AnorexiaCrhr2
Anxiety DisordersCrhr2
Arrhythmias, CardiacAkap9
Arsenic PoisoningAkap9 , Pde4b
Arthritis, JuvenileAdcy7
AsthmaAdcy2 , Crhr2 , Pde4b , Pde4d
Atrial Myxoma, FamilialPrkar1a
Autistic DisorderPde4a , Pde4b
Basal Ganglia DiseasesPde8b
Biliary Tract NeoplasmsPrkacb
Bipolar DisorderPde4b
Birth WeightAdcy5
Brachydactyly with HypertensionPde3a
Brain InjuriesPde4d
Brain IschemiaAkap1 , Prkaca , Prkacb
Breast NeoplasmsAkap12 , Pde2a
BrucellosisPde4a
CarcinomaAdcy5 , Ezr
Carcinoma, Ductal, BreastAkap1
Carcinoma, Renal CellAkap13
Cardiac Complexes, PrematureAkap9
Cardiac Conduction DefectAkap10
CardiomegalyAkap5
CardiomyopathiesAdcy5 , Pde2a
Cardiomyopathy, DilatedAkap9
Cardiomyopathy, HypertrophicAkap9 , Prkaca
Carney ComplexPrkar1a
CholangiocarcinomaPrkaca , Prkacb
Cocaine-Related DisordersCrhr2
ColitisCrhr2
Colonic Diseases, FunctionalCrhr2
colorectal cancerAkap9
Colorectal NeoplasmsAkap9
Cushing SyndromePrkar1a
Deafness, Autosomal Recessive 44Adcy1
Death, Sudden, CardiacAkap9
Depressive DisorderCrhr2 , Pde4d
Diabetes Mellitus, ExperimentalPde3a
Diabetes Mellitus, Type 2Adcy5
Diabetic AngiopathiesAdcy3 , Adcy8
DysarthriaAdcy5 , Pde8b
Dyskinesia, Familial, with Facial MyokymiaAdcy5
DYSKINESIA, LIMB AND OROFACIAL, INFANTILE-ONSETPde10a
Esophageal NeoplasmsAkap13
Fetal HypoxiaCrhr2
FibrosisAdcy5
Genetic Diseases, InbornAdcy5
Glycogen Storage Disease Type IIbAkap14
Granulosa Cell TumorPrkar2b
Heart ArrestAkap9
Heart FailurePrkaca , Prkar2a , Prkar2b
Hypercalciuria, Absorptive, 2Adcy10
HyperkinesisAdcy1 , Adcy8
HypertensionAdcy5 , Crhr2 , Prkar1b
Hypertension, PulmonaryPde3a
Hypertrophy, Left VentricularCrhr2
Hypoglossal Nerve InjuriesPrkaca , Prkacb
HypotensionCrhr2
Infertility, FemaleAdcy3
Infertility, MaleAkap4
InflammationCrhr2
Inflammatory Bowel Disease 11Adcy7
Insulin ResistancePde3a
Irritable Bowel SyndromeCrhr2
IschemiaCrhr2
Ischemic Attack, TransientPde4d
Kartagener SyndromePrkar1b
Learning DisordersPde1b
LETHAL CONGENITAL CONTRACTURE SYNDROME 8Adcy6
Leukemia, Myeloid, AcuteAdcy7 , Pde4b
Leukemia, Promyelocytic, AcutePrkar1a
Liver Cirrhosis, ExperimentalEzr
Long QT SyndromeAkap8 , Akap9
Long QT Syndrome 11Akap9
Long QT Syndrome 2Akap9
Lung DiseasesCrhr2
Mammary Neoplasms, AnimalAdcy5 , Ezr
Mammary Neoplasms, ExperimentalAdcy5 , Ezr
MedulloblastomaPrkar1a
Memory DisordersAkap5
Mineralocorticoid Excess Syndrome, ApparentPrkar1a
Mood DisordersAdcy8 , Adcy9
Motor Skills DisordersAkap5
Muscle RigidityPde8b
Muscular AtrophyCrhr2
Myocardial InfarctionPde3a
Myocardial IschemiaPde4b
MyxomaPrkar1a
Neoplasm MetastasisEzr
Neurodegenerative DiseasesPde8b
Neurodevelopmental DisordersAdcy5
ObesityAkap1 , Prkar2b
Olfaction DisordersAdcy3
OsteoarthritisEzr
OsteoporosisAdcy5
Parkinsonian DisordersAdcy5
Pigmented Nodular Adrenocortical Disease, Primary, 1Prkar1a
Pigmented Nodular Adrenocortical Disease, Primary, 2Pde11a
Pigmented Nodular Adrenocortical Disease, Primary, 3Pde8b
Pigmented Nodular Adrenocortical Disease, Primary, 4Prkaca
Pleomorphic Xanthoastrocytoma Adcy1 , Akap9 , Crhr2 , Pde1c , Prkar2b
PneumoniaCrhr2
Pneumonia, PneumococcalCrhr2
Polycystic Ovary SyndromePde3b
primary ciliary dyskinesiaPrkar1b
prostate cancerAkap1 , Akap2 , Pde1c , Pde3a , Pde7b
Prostatic NeoplasmsAkap1 , Akap13 , Akap2 , Ezr , Pde1c , Pde3a , Pde4d , Pde7b , Prkacb
RhinitisCrhr2
Romano-Ward SyndromeAkap9
SchizophreniaAdcy7 , Pde4b
SeizuresPde4a
Skin DiseasesAkap9 , Pde4b
Small Cell Lung CarcinomaAdcy1
Smith-Magenis SyndromeAkap1 , Akap10 , Prkar1a
Striatal Degeneration, Autosomal DominantPde8b
STRIATAL DEGENERATION, AUTOSOMAL DOMINANT 2Pde10a
StrokePde4d
Substance Withdrawal SyndromeAdcy1 , Adcy8
Substance-Related DisordersAkap7 , Pde1c
Tachycardia, VentricularAkap9
TetanyAkap5
ThrombosisPde3a
Thyroid cancer, papillaryPrkar1a
Ventricular Dysfunction, LeftAdcy5
Ventricular FibrillationAkap9
Weight GainAkap2
Pathway Annotations Associated with Genes in the protein kinase A (PKA) signaling pathway
Pathway TermsGene Symbols
acebutolol pharmacodynamics pathwayPrkaca , Prkar1a
adenine phoshoribosyltransferase deficiency pathwayAdcy10 , Pde10a , Pde4d
adenosine monophosphate deaminase deficiency pathwayAdcy10 , Pde10a , Pde4d
adenosine signaling pathwayAdcy2 , Prkacb
adenylosuccinate lyase deficiency pathwayAdcy10 , Pde10a , Pde4d
adrenergic beta receptor agonist and beta-blocker pharmacodynamics pathwayPrkaca , Prkar1a
AICA-ribosuria pathwayAdcy10 , Pde10a , Pde4d
amiodarone pharmacodynamics pathwayPrkaca , Prkar1a
amlodipine pharmacodynamics pathwayPrkaca , Prkar1a
apoptotic cell death pathwayPrkaca , Prkacb , Prkar1a , Prkar2a , Prkar2b
atenolol pharmacodynamics pathwayPrkaca , Prkar1a
azathioprine pharmacodynamics pathwayAdcy10 , Pde10a , Pde4d
betaxolol pharmacodynamics pathwayPrkaca , Prkar1a
bile acid transport pathwayAdcy1 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Prkaca , Prkacb
bisoprolol pharmacodynamics pathwayPrkaca , Prkar1a
bupranolol drug pathwayPrkaca , Prkar1a
bupranolol pharmacodynamics pathwayPrkaca , Prkar1a
calcium/calcium-mediated signaling pathwayAdcy1 , Adcy2 , Adcy3 , Adcy4 , Adcy7 , Adcy8 , Adcy9 , Pde1a , Pde1b , Pde1c , Prkaca , Prkacb
carvedilol pharmacodynamics pathwayPrkaca , Prkar1a
chemokine mediated signaling pathwayAdcy1 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Prkaca , Prkacb
cilostazol pharmacodynamics pathwayPde4d
corticotropin-releasing hormone signaling pathwayCrhr2
dilated cardiomyopathy pathwayAdcy1 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Prkaca , Prkacb
diltiazem pharmacodynamics pathwayPrkaca , Prkar1a
dipyridamole pharmacodyamics pathwayPde4d
disopyramide pharmacodynamics pathwayPrkaca , Prkar1a
dobutamine pharmacodynamics pathwayPrkaca , Prkar1a
dopamine signaling pathwayPrkaca , Prkacb
dopamine signaling pathway via D1 family of receptorsAdcy2 , Adcy5 , Prkacb
dopamine signaling pathway via D2 family of receptorsAdcy5
eicosanoid signaling pathwayPrkaca
endothelin signaling pathwayAdcy1 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8
Entamoeba histolyca infection pathwayAdcy1 , Prkaca , Prkacb
esmolol pharmacodynamics pathwayPrkaca , Prkar1a
FasL mediated signaling pathwayEzr
flecainde pharmacodynamics pathwayPrkaca , Prkar1a
follicle-stimulating hormone signaling pathwayAdcy2 , Prkacb
fosphenytoin pharmacodynamics pathwayPrkaca , Prkar1a
G protein mediated signaling pathway via Galphai familyAdcy5
G protein mediated signaling pathway via Galphas familyAdcy1 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Crhr2
glucagon signaling pathwayAdcy5 , Adcy6
glutamate signaling pathwayAdcy1 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Prkaca , Prkacb
gonadotropin-releasing hormone signaling pathwayAdcy1 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Prkaca , Prkacb
granulocyte-macrophage colony-stimulating factor signaling pathwayPrkaca , Prkacb
Hedgehog signaling pathwayPrkaca , Prkacb
histamine signaling pathway, immunologicalAdcy2 , Prkacb
ibutilide pharmacodynamics pathwayPrkaca , Prkar1a
insulin signaling pathwayPde3a , Pde3b , Prkaca , Prkacb , Prkar1a , Prkar2a , Prkar2b
interleukin-3 signaling pathwayPrkaca , Prkacb
isoprenaline pharmacodynamics pathwayPrkaca , Prkar1a
isradipine pharmacodynamics pathwayPrkaca , Prkar1a
Kelley-Seegmiller syndrome pathwayAdcy10 , Pde10a , Pde4d
Lesch-Nyhan syndrome pathwayAdcy10 , Pde10a , Pde4d
levobunolol pharmacodynamics pathwayPrkaca , Prkar1a
lidocaine pharmacodynamics pathwayPrkaca , Prkar1a
long term potentiationAdcy1 , Adcy8 , Prkaca , Prkacb
luteinizing hormone signaling pathwayAdcy2 , Prkacb
melanocortin system pathwayAdcy2 , Prkacb
mercaptopurine pharmacodynamics pathwayAdcy10 , Pde10a , Pde4d
metoprolol pharmacodynamics pathwayPrkaca , Prkar1a
mexiletine pharmacodynamics pathwayPrkaca , Prkar1a
mitogen activated protein kinase signaling pathwayPrkaca , Prkacb
molybdenum cofactor deficiency pathwayAdcy10 , Pde10a , Pde4d
nadolol pharmacodynamics pathwayPrkaca , Prkar1a
nebivolol pharmacodynamics pathwayPrkaca , Prkar1a
nifedipine pharmacodynamics pathwayPrkaca , Prkar1a
nimodipine pharmacodynamics pathwayPrkaca , Prkar1a
nisoldipine pharmacodynamics pathwayPrkaca , Prkar1a
nitrendipine pharmacodynamics pathwayPrkaca , Prkar1a
parathyroid hormone signaling pathwayEzr
penbutolol pharmacodynamics pathwayPrkaca , Prkar1a
phenytoin pharmacodynamics pathwayPrkaca , Prkar1a
phosphatidylinositol 3-kinase-Akt signaling pathwayPrkaca
pindolol pharmacodynamics pathwayPrkaca , Prkar1a
prion diseases pathwayPrkaca , Prkacb
procainamide pharmacodynamics pathwayPrkaca , Prkar1a
propranolol pharmacodynamics pathwayPrkaca , Prkar1a
prostaglandin D2 signaling pathwayAdcy2 , Prkacb
prostaglandin I2 signaling pathwayAdcy2 , Prkacb
protein kinase A (PKA) signaling pathwayAdcy1 , Adcy10 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Akap1 , Akap10 , Akap11 , Akap12 , Akap13 , Akap14 , Akap2 , Akap3 , Akap4 , Akap5 , Akap6 , Akap7 , Akap8 , Akap9 , Crhr2 , Ezr , Pde10a , Pde11a , Pde1a , Pde1b , Pde1c , Pde2a , Pde3a , Pde3b , Pde4a , Pde4b , Pde4c , Pde4d , Pde7a , Pde7b , Pde8a , Pde8b , Prkaca , Prkacb , Prkar1a , Prkar1b , Prkar2a , Prkar2b
purine metabolic pathwayAdcy1 , Adcy10 , Adcy2 , Adcy3 , Adcy4 , Adcy5 , Adcy6 , Adcy7 , Adcy8 , Adcy9 , Pde10a , Pde11a , Pde1a , Pde1b , Pde1c , Pde2a , Pde3a , Pde3b , Pde4a , Pde4b , Pde4c , Pde4d , Pde7a , Pde7b , Pde8a , Pde8b
purine nucleoside phosphorylase deficiency pathwayAdcy10 , Pde10a , Pde4d
quinidine pharmacodynamics pathwayPrkaca , Prkar1a
serotonin signaling pathway via receptors engaging G alphas protein familyAdcy2 , Prkacb
sotalol pharmacodynamics pathwayPrkaca , Prkar1a
syndecan signaling pathwayEzr , Prkaca
timolol pharmacodynamics pathwayPrkaca , Prkar1a
tioguanine pharmacodynamics pathwayAdcy10 , Pde10a , Pde4d
Trypanosoma cruzi infection pathwayAdcy1
vascular endothelial growth factor signaling pathwayAkap1 , Prkaca
vasopressin signaling pathwayAdcy6 , Akap7 , Pde4d
vasopressin signaling pathway via receptor type 2Adcy2 , Adcy3 , Adcy6 , Adcy9 , Akap7 , Pde4d , Prkaca , Prkacb
verapamil pharmacodynamics pathwayPrkaca , Prkar1a
Wnt signaling pathwayPrkaca , Prkacb
xanthinuria disease pathwayAdcy10 , Pde10a , Pde4d
xanthinuria disease pathway, type IAdcy10 , Pde10a , Pde4d
xanthinuria disease pathway, type IIAdcy10 , Pde10a , Pde4d
Phenotype Annotations Associated with Genes in the protein kinase A (PKA) signaling pathway

References Associated with the protein kinase A (PKA) signaling pathway:

Ontology Path Diagram:

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Import into Pathway Studio: