Autocrine regulation of airway smooth muscle contraction by diacylglycerol kinase.
DGK
GPCR
asthma
calcium
cyclooxygenase
smooth muscle
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
01
07
2021
received:
12
03
2021
accepted:
06
07
2021
pubmed:
20
7
2021
medline:
6
5
2022
entrez:
19
7
2021
Statut:
ppublish
Résumé
Diacylglycerol kinase (DGK), a lipid kinase, catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid, thereby terminating DAG-mediated signaling by Gq-coupled receptors that regulate contraction of airway smooth muscle (ASM). A previous study from our laboratory demonstrated that DGK inhibition or genetic ablation leads to reduced ASM contraction and provides protection for allergen-induced airway hyperresponsiveness. However, the mechanism by which DGK regulates contractile signaling in ASM is not well established. Herein, we investigated the role of prorelaxant cAMP-protein kinase A (PKA) signaling in DGK-mediated regulation of ASM contraction. Pretreatment of human ASM cells with DGK inhibitor I activated PKA as demonstrated by the phosphorylation of PKA substrates, VASP, Hsp20, and CREB, which was abrogated when PKA was inhibited pharmacologically or molecularly using overexpression of the PKA inhibitor peptide, PKI. Furthermore, inhibition of DGK resulted in induction of cyclooxygenase (COX) and generation of prostaglandin E
Identifiants
pubmed: 34278583
doi: 10.1002/jcp.30528
pmc: PMC8763953
mid: NIHMS1722525
doi:
Substances chimiques
Diacylglycerol Kinase
EC 2.7.1.107
Cyclic AMP-Dependent Protein Kinases
EC 2.7.11.11
Protein Kinase C
EC 2.7.11.13
Dinoprostone
K7Q1JQR04M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
603-616Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL058506
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL114471
Pays : United States
Organisme : NHLBI NIH HHS
ID : R29 HL058506
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL058506
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146645
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL146645
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL137030
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137030
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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