ArticleScientific reports2019
Phosphorylation Changes in Response to Kinase Inhibitor H89 in PKA-Null Cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
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- Selective targeting of IRAK1 attenuates low molecular weight hyaluronic acid-induced stemness and non-canonical STAT3 activation in epithelial ovarian cancer.Cell death & disease · 2024Article
- Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids.Molecular cancer research : MCR · 2024Article
- Hypertonicity during a rapid rise in D-glucose mediates first-phase insulin secretion.Frontiers in endocrinology · 2024Article
- Apremilast-induced increases in acute ethanol intoxication and decreases in ethanol drinking in mice involve PKA phosphorylation of GABANeuropharmacology · 2022Article
- KOPI: Kinase inhibitOr Proteome Impact analysis.Scientific reports · 2022Article
- Distinct PKA Signaling in Cytosolic and Mitochondrial Compartments in Electrically Paced Atrial Myocytes.Cells · 2022Article
- Anti-Hair Loss Effect of Adenosine Is Exerted by cAMP Mediated Wnt/β-Catenin Pathway Stimulation via Modulation of Gsk3β Activity in Cultured Human Dermal Papilla Cells.Molecules (Basel, Switzerland) · 2022Article
- C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation.The EMBO journal · 2022Article
- Glucocorticoid Receptor Maintains Vasopressin Responses in Kidney Collecting Duct Cells.Frontiers in physiology · 2022Article
- Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity.Frontiers in bioengineering and biotechnology · 2022Article
- Aquaporin 2 regulation: implications for water balance and polycystic kidney diseases.Nature reviews. Nephrology · 2021Review
- Article
- The Small Molecule H89 InhibitsInfection and immunity · 2021Article
- cAMP signaling through protein kinase A and Epac2 induces substance P release in the rat spinal cord.Neuropharmacology · 2021Article
- Phosphoproteomic Identification of Vasopressin/cAMP/Protein Kinase A-Dependent Signaling in Kidney.Molecular pharmacology · 2021Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Protein phosphorylation, mediated by protein kinases, plays a crucial role in cellular regulation. One of the most important protein kinases is protein kinase A (PKA). N-[2-p-bromocinnamylamino-ethyl]-5-isoquinolinesulphonamide (H89) is often used as a "PKA specific inhibitor" to study the involvement of PKA in signaling pathways. However, evidence from cell-free experiments has suggested that H89 can also inhibit other protein kinases. In this study, previously generated PKA-null and PKA-intact mouse cell lines derived from mpkCCD cells were treated with H89 over a range of concentrations commonly used in the literature, followed by mass spectrometry-based phosphoproteomics to globally assess changes in phosphorylation. From a total of 14,139 phosphorylation sites quantified, we found that 571 and 263 phosphorylation sites with significant changes in abundance in PKA-intact and PKA-null cells, respectively. Analyses of sequence logos generated from significantly decreased phosphorylation sites in PKA-intact and PKA-null cells both revealed a preference for basic amino acids at position -3 and -2. Thus, H89 appears to inhibit basophilic kinases even in the absence of PKA. Likely H89 targets include basophilic protein kinases such as AKT, RSK, AMPK and ROCK. We conclude that, in intact cells, H89 can affect activities of protein kinases other than PKA, and therefore responses to H89 should not be regarded as sufficient evidence for PKA involvement in a signaling process.
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