Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110 (AKAP110) mediates camp-independent PKA activation

Jiaxin Niu, Rita Vaiskunaite, Nobuchika Suzuki, Tohru Kozasa, Daniel W. Carr, Nickolai Dulin, Tatyana A. Voyno-Yasenetskaya

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Heterotrimeric G proteins [1] and protein kinase A (PKA) are two important transmitters that transfer signals from a wide variety of cell surface receptors to generate physiological responses. The established mechanism of PKA activation involves the activation of the Gs-cAMP pathway [2]. Binding of cAMP to the regulatory subunit of PKA (rPKA) leads to a release and subsequent activation of a catalytic subunit of PKA (cPKA). Here, we report a novel mechanism of PKA stimulation that does not require cAMP. Using yeast two-hybrid screening, we found that the α subunit of G13 protein interacted with a member of the PKA-anchoring protein family, AKAP110. Using in vitro binding and coimmunoprecipitation assays, we have shown that only activated Gα13 binds to AKAP110, suggesting a potential role for AKAP110 as a Gα subunit effector protein. Importantly, Gα13, AKAP110, rPKA, and cPKA can form a complex, as shown by coimmunoprecipitation. By characterizing the functional significance of the Gα13-AKAP110 interaction, we have found that Gα13 induced release of the cPKA from the AKAP110-rPKA complex, resulting in a cAMP-independent PKA activation. Finally, AKAP110 significantly potentiated Gα13-induced activation of PKA. Thus, AKAP110 provides a link between heterotrimeric G proteins and cAMP-independent activation of PKA.

Original languageEnglish (US)
Pages (from-to)1686-1690
Number of pages5
JournalCurrent Biology
Volume11
Issue number21
DOIs
StatePublished - Oct 30 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110 (AKAP110) mediates camp-independent PKA activation'. Together they form a unique fingerprint.

  • Cite this