Autocrine regulation of airway smooth muscle contraction by diacylglycerol kinase.
Publication/Presentation Date
1-1-2022
Abstract
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
Volume
237
Issue
1
First Page
603
Last Page
616
ISSN
1097-4652
Published In/Presented At
Yadav, S. K., Sharma, P., Shah, S. D., Panettieri, R. A., Kambayashi, T., Penn, R. B., & Deshpande, D. A. (2022). Autocrine regulation of airway smooth muscle contraction by diacylglycerol kinase. Journal of cellular physiology, 237(1), 603–616. https://doi.org/10.1002/jcp.30528
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
34278583
Department(s)
Administration and Leadership
Document Type
Article