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 Carr, Nickolai Dulin, Tatyana A. Voyno-Yasenetskaya

Research output: Contribution to journalArticle

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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

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G12-G13 GTP-Binding Protein alpha Subunits
cAMP-dependent protein kinase
Cyclic AMP-Dependent Protein Kinases
protein kinases
Protein Kinases
Phosphotransferases
Chemical activation
protein subunits
Proteins
proteins
Heterotrimeric GTP-Binding Proteins
regulatory proteins
G-proteins
Catalytic Domain
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
two hybrid system techniques
Protein Subunits
Cell Surface Receptors
physiological response
Yeasts

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110 (AKAP110) mediates camp-independent PKA activation. / Niu, Jiaxin; Vaiskunaite, Rita; Suzuki, Nobuchika; Kozasa, Tohru; Carr, Daniel; Dulin, Nickolai; Voyno-Yasenetskaya, Tatyana A.

In: Current Biology, Vol. 11, No. 21, 30.10.2001, p. 1686-1690.

Research output: Contribution to journalArticle

Niu, Jiaxin ; Vaiskunaite, Rita ; Suzuki, Nobuchika ; Kozasa, Tohru ; Carr, Daniel ; Dulin, Nickolai ; Voyno-Yasenetskaya, Tatyana A. / Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110 (AKAP110) mediates camp-independent PKA activation. In: Current Biology. 2001 ; Vol. 11, No. 21. pp. 1686-1690.
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