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STK25 inhibits PKA signaling by phosphorylating PRKAR1A.

ABSTRACT: In the heart, protein kinase A (PKA) is critical for activating calcium handling and sarcomeric proteins in response to beta-adrenergic stimulation leading to increased myocardial contractility and performance. The catalytic activity of PKA is tightly regulated by regulatory subunits that inhibit the catalytic subunit until released by cAMP binding. Phosphorylation of type II regulatory subunits promotes PKA activation; however, the role of phosphorylation in type I regulatory subunits remain uncertain. Here, we utilize human induced pluripotent stem cell cardiomyocytes (iPSC-CMs) to identify STK25 as a kinase of the type Iα regulatory subunit PRKAR1A. Phosphorylation of PRKAR1A leads to inhibition of PKA kinase activity and increased binding to the catalytic subunit in the presence of cAMP. Stk25 knockout in mice diminishes Prkar1a phosphorylation, increases Pka activity, and augments contractile response to beta-adrenergic stimulation. Together, these data support STK25 as a negative regulator of PKA signaling through phosphorylation of PRKAR1A.

SUBMITTER: Zhang X

PROVIDER: S-EPMC9446420 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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STK25 inhibits PKA signaling by phosphorylating PRKAR1A.

Zhang Xiaokan X Wang Bryan Z BZ Kim Michael M Nash Trevor R TR Liu Bohao B Rao Jenny J Lock Roberta R Tamargo Manuel M Soni Rajesh Kumar RK Belov John J Li Eric E Vunjak-Novakovic Gordana G Fine Barry B

Cell reports 20220801 7

In the heart, protein kinase A (PKA) is critical for activating calcium handling and sarcomeric proteins in response to beta-adrenergic stimulation leading to increased myocardial contractility and performance. The catalytic activity of PKA is tightly regulated by regulatory subunits that inhibit the catalytic subunit until released by cAMP binding. Phosphorylation of type II regulatory subunits promotes PKA activation; however, the role of phosphorylation in type I regulatory subunits remain un ...[more]

PMID: 35977512

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STK25 inhibits PKA signaling by phosphorylating PRKAR1A.

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STK25 inhibits PKA signaling by phosphorylating PRKAR1A.

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