High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A,MmPDE8,Mouse,Mus musculus,Pde8,Pde8a
- Known as:
- High antigenic cAMP-specific IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A,MmPDE8,Mouse,Mus musculus,Pde8,Pde8a
- Catalog number:
- EIAAB30351
- Category:
- -
- Supplier:
- EIAab
- Gene target:
- High affinity cAMP-specific and IBMX-insensitive 3' 5'-cyclic phosphodiesterase 8A MmPDE8 Mouse Mus musculus Pde8 Pde8a
Ask about this productRelated genes to: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A,MmPDE8,Mouse,Mus musculus,Pde8,Pde8a
- Gene:
- PDE8A NIH gene
- Name:
- phosphodiesterase 8A
- Previous symbol:
- -
- Synonyms:
- HsT19550
- Chromosome:
- 15q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-06-12
- Date modifiied:
- 2014-11-19
Related products to: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A,MmPDE8,Mouse,Mus musculus,Pde8,Pde8a
Related articles to: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A,MmPDE8,Mouse,Mus musculus,Pde8,Pde8a
- Pancreatic ductal adenocarcinoma (PDAC) is considered the third leading cause of cancer mortality in the western world, offering advanced stage patients with few viable treatment options. Consequently, there remains an urgent unmet need to develop novel therapeutic strategies that can effectively inhibit pro-oncogenic molecular targets underpinning PDACs pathogenesis and progression. One such target is c-RAF, a downstream effector of RAS that is considered essential for the oncogenic growth and survival of mutant RAS-driven cancers (including KRAS PDAC). Herein, we demonstrate how a novel cell-penetrating peptide disruptor (DRx-170) of the c-RAF-PDE8A protein-protein interaction (PPI) represents a differentiated approach to exploiting the c-RAF-cAMP/PKA signaling axes and treating KRAS-c-RAF dependent PDAC. Through disrupting the c-RAF-PDE8A protein complex, DRx-170 promotes the inactivation of c-RAF through an allosteric mechanism, dependent upon inactivating PKA phosphorylation. DRx-170 inhibits cell proliferation, adhesion and migration of a KRAS PDAC cell line (PANC1), independent of ERK1/2 activity. Moreover, combining DRx-170 with afatinib significantly enhances PANC1 growth inhibition in both 2D and 3D cellular models. DRx-170 sensitivity appears to correlate with c-RAF dependency. This proof-of-concept study supports the development of DRx-170 as a novel and differentiated strategy for targeting c-RAF activity in KRAS-c-RAF dependent PDAC. - Source: PubMed
Publication date: 2024/04/18
Cooke Sean FWright Thomas ASin Yuan YanLing JiayueKyurkchieva ElkaPhanthaphol NattapornMcskimming ThomasHerbert KatharineRebus SelmaBiankin Andrew VChang David KBaillie George SBlair Connor M - - Source: PubMed
Publication date: 2024/04/11
Subramanian HariharanNikolaev Viacheslav O - The expression of phosphodiesterase 7A (PDE7A) and phosphodiesterase 8A (PDE8) genes is integral to human signaling pathways, and the inhibition of PDE7A has been associated with the onset of various diseases, including effects on the immune system and nervous system. The development of PDE7 selective inhibitors can promote research on immune and nervous system diseases, such as multiple sclerosis, chronic inflammation, and autoimmune responses. PDE8A is expressed alongside PDE8B, and its inhibitory mechanism is still unclear. Studying the mechanisms of selective inhibitors against different PDE subtypes is crucial to prevent potential side effects, such as nausea and cardiac toxicity, and the sequence similarity of the two protein subtypes was 55.9%. Therefore, it is necessary to investigate the differences of both subtypes' ligand binding sites. Selective inhibitors of two proteins were chosen to summarize the reason for their selectivity through molecular docking, molecular dynamics simulation, alanine scanning mutagenesis, and MM-GBSA calculation. We found that Phe384, Leu401, Gln413, Tyr419, and Phe416 in the active site positively contribute to the selectivity towards PDE7A. Additionally, Asn729, Phe767, Gln778, and Phe781 positively contribute to the selectivity towards PDE8A. - Source: PubMed
Publication date: 2024/04/17
Wang ZhijianWang ShizunWang HanxunHu BaichunQi ZhuoZhang YamingSong PengfeiCai QingkuiYang HualiWang Jian - In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3',5'-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases). Several AKAPs (A kinase anchoring proteins) regulate cardiac function and are proposed as targets for precise pharmacology. AKAP12 is expressed in the heart and has been reported to directly bind β2-adrenergic receptor, PKA, and PDE4D. However, its roles in cardiac function are unclear. - Source: PubMed
Publication date: 2024/03/20
Qasim HananRajaei MehrdadXu YingReyes-Alcaraz ArfaxadAbdelnasser Hala YStewart M DavidLahiri Satadru KWehrens Xander H TMcConnell Bradley K - The cAMP/PKA and mitogen-activated protein kinase (MAPK) signaling cascade control many cellular processes and are highly regulated for optimal cellular responses upon external stimuli. Phosphodiesterase 8A (PDE8A) is an important regulator that inhibits signaling via cAMP-dependent PKA by hydrolyzing intracellular cAMP pool. Conversely, PDE8A activates the MAPK pathway by protecting CRAF/Raf1 kinase from PKA-mediated inhibitory phosphorylation at Ser259 residue, a binding site of scaffold protein 14-3-3. It still remains enigmatic as to how the cross-talk involving PDE8A regulation influences cAMP/PKA and MAPK signaling pathways. Here, we report that PDE8A interacts with 14-3-3ζ in both yeast and mammalian system, and this interaction is enhanced upon the activation of PKA, which phosphorylates PDE8A's Ser359 residue. Biophysical characterization of phospho-Ser359 peptide with 14-3-3ζ protein further supports their interaction. Strikingly, 14-3-3ζ reduces the catalytic activity of PDE8A, which upregulates the cAMP/PKA pathway while the MAPK pathway is downregulated. Moreover, 14-3-3ζ in complex with PDE8A and cAMP-bound regulatory subunit of PKA, RIα, delays the deactivation of PKA signaling. Our results define 14-3-3ζ as a molecular switch that operates signaling between cAMP/PKA and MAPK by associating with PDE8A. - Source: PubMed
Publication date: 2024/02/06
Mukherjee SoumitaRoy SomeshMukherjee ShrutiHarikishore AmaravadhiBhunia AnirbanMandal Atin K