A 2B adenosine receptor activation and modulation by protein kinase C.

Autor: Gao ZG; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA., Levitan IM; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA., Inoue A; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan., Wei Q; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA., Jacobson KA; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Jazyk: angličtina
Zdroj: IScience [iScience] 2023 Jun 19; Vol. 26 (7), pp. 107178. Date of Electronic Publication: 2023 Jun 19 (Print Publication: 2023).
DOI: 10.1016/j.isci.2023.107178
Abstrakt: Protein kinase C (PKC) isoforms regulate many important signaling pathways. Here, we report that PKC activation by phorbol 12-myristate 13-acetate (PMA) enhanced A 2B adenosine receptor (AR)-mediated, but not β 2 -adrenergic receptor-mediated, cAMP accumulation, in H9C2 cardiomyocyte-like and HEK293 cells. In addition to enhancement, PKC (PMA-treatment) also activated A 2B AR with low E max (H9C2 and NIH3T3 cells endogenously expressing A 2B AR), or with high E max (A 2B AR-overexpressing HEK293 cells) to induce cAMP accumulation. A 2B AR activation induced by PKC was inhibited by A 2B AR and PKC inhibitors but enhanced by A 2B AR overexpression. Gαi isoforms and PKCγ isoform were found to be involved in both enhancement of A 2B AR function and A 2B AR activation. Thus, we establish PKC as an endogenous modulator and activator of A 2B AR, involving G iα and PKCγ. Depending on signaling pathway, PKC could activate and enhance, or alternatively inhibit A 2B AR activity. These findings are relevant to common functions of A 2B AR and PKC, e.g. cardioprotection and cancer progression/treatment.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Databáze: MEDLINE
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