Novel function of the regulatory subunit of protein kinase A: Regulation of cytochrome c oxidase activity and cytochrome c release

Weng Lang Yang, Lisa Iacono, Wei Min Tang, Khew Voon Chin

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

There have been speculations that the regulatory (R) subunit of the cAMP-dependent protein kinase (PKA) may have other functions. A recent study has shown that the catalytic (C) subunit of PKA may be regulated in a cAMP- and R subunit-independent manner. However, evidence linking a function to the R subunit apart from inhibiting the C subunit has been elusive. In this report, interaction cloning experiments showed that the RIα subunit association with the cytochrome c oxidase subunit Vb (CoxVb) is cAMP- sensitive. Interaction was detected with a GST-RIα fusion protein as well as by coimmunoprecipitation. Transient treatment with cAMP-elevating agents inhibited cytochrome c oxidase in Chinese hamster ovary (CHO) cells with a concomitant decrease in cytochrome c levels in the mitochondria and an increase in its release into the cytosol. Furthermore, mutant cells harboring a defective RIα show increased cytochrome c oxidase activity and also constitutively lower levels of cytochrome c in comparison to either the wild- type cells or the C subunit mutant. These results suggest a novel mechanism of cAMP signaling through the interaction of Riot with CoxVb thereby regulating cytochrome c oxidase activity as well as the cytochrome c levels.

Original languageEnglish (US)
Pages (from-to)14175-14180
Number of pages6
JournalBiochemistry
Volume37
Issue number40
DOIs
StatePublished - Oct 6 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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