FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4285602583> ?p ?o ?g. }

• W4285602583 endingPage "819" @default.
• W4285602583 startingPage "806" @default.
• W4285602583 abstract "Salt-inducible kinases (SIK1–3) are serine/threonine protein kinases that target several effector molecules implicated in the regulation of a variety of cellular processes including metabolism, inflammation, and cancer. Recent advances in the mechanistic understanding of pulmonary arterial hypertension (PAH) suggest a critical role for deregulated signaling pathways in patients and animal models. Multiple lines of evidence support functional parallels between SIK-regulated pathways in tumorigenesis, inflammation, and PAH. A better understanding of SIK functions and downstream targets may unlock the potential of SIKs as promising therapeutic targets for the development of much-needed therapies for PAH. Salt-inducible kinases (SIKs) are serine/threonine kinases belonging to the AMP-activated protein kinase (AMPK) family. Accumulating evidence indicates that SIKs phosphorylate multiple targets, including histone deacetylases (HDACs) and cAMP response element-binding protein (CREB)-regulated transcriptional coactivators (CRTCs), to coordinate signaling pathways implicated in metabolism, cell growth, proliferation, apoptosis, and inflammation. These pathways downstream of SIKs are altered not only in pathologies like cancer, systemic hypertension, and inflammatory diseases, but also in pulmonary arterial hypertension (PAH), a multifactorial disease characterized by pulmonary vasoconstriction, inflammation and remodeling of pulmonary arteries owing to endothelial dysfunction and aberrant proliferation of smooth muscle cells (SMCs). In this opinion article, we present evidence of SIKs as modulators of key signaling pathways involved in PAH pathophysiology and discuss the potential of SIKs as therapeutic targets for PAH, emphasizing the need for deeper molecular insights on PAH. Salt-inducible kinases (SIKs) are serine/threonine kinases belonging to the AMP-activated protein kinase (AMPK) family. Accumulating evidence indicates that SIKs phosphorylate multiple targets, including histone deacetylases (HDACs) and cAMP response element-binding protein (CREB)-regulated transcriptional coactivators (CRTCs), to coordinate signaling pathways implicated in metabolism, cell growth, proliferation, apoptosis, and inflammation. These pathways downstream of SIKs are altered not only in pathologies like cancer, systemic hypertension, and inflammatory diseases, but also in pulmonary arterial hypertension (PAH), a multifactorial disease characterized by pulmonary vasoconstriction, inflammation and remodeling of pulmonary arteries owing to endothelial dysfunction and aberrant proliferation of smooth muscle cells (SMCs). In this opinion article, we present evidence of SIKs as modulators of key signaling pathways involved in PAH pathophysiology and discuss the potential of SIKs as therapeutic targets for PAH, emphasizing the need for deeper molecular insights on PAH. heterotrimeric enzyme that functions as a cellular metabolic regulator and energy sensor. On ATP depletion, it inactivates anabolic ATP-consuming pathways and activates catabolic ATP-generating processes. It is also activated by several hormones and cytokines. Inactivates a number of metabolic enzymes involved in ATP-consuming cellular events including fatty acid, cholesterol and protein synthesis, and activates ATP-generating processes. increase CREB activity, promoting cell proliferation, differentiation, and metabolic switch, and for that reason play a key role in tumor progression and resistance to chemotherapy. repressors of transcription factors like MEF2, regulating physiological and pathological mechanisms such as those related to bone formation, vascular calcification, or leukemia. enzyme responsible for most of the NO produced in the vasculature. The NO is crucial for the regulation of vascular tone and cellular proliferation and migration, as well as leukocyte adhesion and platelet aggregation. Endothelial dysfunction associated with PAH is characterized by impaired NO production by eNOS. mechanism by which ECs lose cell-to-cell contact and undergo transition towards a mesenchymal-like phenotype. This comes with loss of endothelial markers, like vascular endothelial (VE)-cadherin and PECAM-1, and the gain of myofibroblast markers such α-SMA and vimentin. serine/threonine protein kinase that regulates cell metabolism, proliferation, and migration and is known to function as a tumor suppressor. transmembrane protein responsible for maintaining high cytosolic potassium concentration and low cytosolic sodium concentration. NKA is crucial to keep a negative resting membrane potential and provide a driving force for secondary ion transport, while it simultaneously works as a signal transducer in multiple pathways. Its expression and function are essential for the regulation of vasculature contractility. In pulmonary arteries, hypoxia inhibits NKA, leading to membrane depolarization and consequent opening of calcium channels, which culminates in vasoconstriction. a ubiquitous transcription factor that regulates the expression of genes involved in inflammation, innate immunity, stress responses, cell proliferation, and survival. Increased NF-κB activity promotes the expression of proinflammatory cytokines and chemokines, antiapoptotic factors, cell-cycle regulators, and adhesion molecules. NF-κB expression is increased in the lungs of PAH rodent models and activated in the pulmonary vessels of PAH patients. It is recognized as a key proinflammatory factor in the development of PAH." @default.
• W4285602583 created "2022-07-16" @default.
• W4285602583 creator A5028281009 @default.
• W4285602583 creator A5057581263 @default.
• W4285602583 creator A5077801823 @default.
• W4285602583 creator A5078712323 @default.
• W4285602583 date "2022-10-01" @default.
• W4285602583 modified "2023-10-15" @default.
• W4285602583 title "Salt-inducible kinases: new players in pulmonary arterial hypertension?" @default.
• W4285602583 cites W1975060439 @default.
• W4285602583 cites W1979954613 @default.
• W4285602583 cites W1998186535 @default.
• W4285602583 cites W2011477996 @default.
• W4285602583 cites W2024338340 @default.
• W4285602583 cites W2027838253 @default.
• W4285602583 cites W2032033480 @default.
• W4285602583 cites W2071690740 @default.
• W4285602583 cites W2079331198 @default.
• W4285602583 cites W2089102722 @default.
• W4285602583 cites W2108744963 @default.
• W4285602583 cites W2131299836 @default.
• W4285602583 cites W2142503372 @default.
• W4285602583 cites W2143209738 @default.
• W4285602583 cites W2151313405 @default.
• W4285602583 cites W2156991338 @default.
• W4285602583 cites W2158140000 @default.
• W4285602583 cites W2282032443 @default.
• W4285602583 cites W2331048077 @default.
• W4285602583 cites W2340923921 @default.
• W4285602583 cites W2399913538 @default.
• W4285602583 cites W2401919281 @default.
• W4285602583 cites W2479584244 @default.
• W4285602583 cites W2492481324 @default.
• W4285602583 cites W2526078391 @default.
• W4285602583 cites W2560815110 @default.
• W4285602583 cites W2592714610 @default.
• W4285602583 cites W2603755769 @default.
• W4285602583 cites W2605198288 @default.
• W4285602583 cites W2621496307 @default.
• W4285602583 cites W2764185374 @default.
• W4285602583 cites W2777517924 @default.
• W4285602583 cites W2777572536 @default.
• W4285602583 cites W2888508916 @default.
• W4285602583 cites W2898766522 @default.
• W4285602583 cites W2904180601 @default.
• W4285602583 cites W2914105091 @default.
• W4285602583 cites W2925191895 @default.
• W4285602583 cites W2946328073 @default.
• W4285602583 cites W2946646116 @default.
• W4285602583 cites W2949173269 @default.
• W4285602583 cites W2964583576 @default.
• W4285602583 cites W2966596554 @default.
• W4285602583 cites W2971757224 @default.
• W4285602583 cites W2988983126 @default.
• W4285602583 cites W2990095932 @default.
• W4285602583 cites W3000332637 @default.
• W4285602583 cites W3000949338 @default.
• W4285602583 cites W3004782517 @default.
• W4285602583 cites W3006378540 @default.
• W4285602583 cites W3045720050 @default.
• W4285602583 cites W3048511516 @default.
• W4285602583 cites W3091861861 @default.
• W4285602583 cites W3093388198 @default.
• W4285602583 cites W3093557098 @default.
• W4285602583 cites W3118583265 @default.
• W4285602583 cites W3125640708 @default.
• W4285602583 cites W3130313437 @default.
• W4285602583 cites W3156666541 @default.
• W4285602583 cites W3163853203 @default.
• W4285602583 cites W3164167898 @default.
• W4285602583 cites W3165523810 @default.
• W4285602583 cites W3173166079 @default.
• W4285602583 cites W3182187705 @default.
• W4285602583 cites W3186904131 @default.
• W4285602583 cites W3201779203 @default.
• W4285602583 cites W3216676365 @default.
• W4285602583 cites W4223519317 @default.
• W4285602583 doi "https://doi.org/10.1016/j.tips.2022.06.008" @default.
• W4285602583 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35851157" @default.
• W4285602583 hasPublicationYear "2022" @default.
• W4285602583 type Work @default.
• W4285602583 citedByCount "4" @default.
• W4285602583 countsByYear W42856025832022 @default.
• W4285602583 countsByYear W42856025832023 @default.
• W4285602583 crossrefType "journal-article" @default.
• W4285602583 hasAuthorship W4285602583A5028281009 @default.
• W4285602583 hasAuthorship W4285602583A5057581263 @default.
• W4285602583 hasAuthorship W4285602583A5077801823 @default.
• W4285602583 hasAuthorship W4285602583A5078712323 @default.
• W4285602583 hasConcept C11960822 @default.
• W4285602583 hasConcept C184235292 @default.
• W4285602583 hasConcept C203014093 @default.
• W4285602583 hasConcept C2776414213 @default.
• W4285602583 hasConcept C2776914184 @default.
• W4285602583 hasConcept C502942594 @default.
• W4285602583 hasConcept C62478195 @default.
• W4285602583 hasConcept C86803240 @default.
• W4285602583 hasConcept C95444343 @default.

• next