TY - JOUR
T1 - Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110 (AKAP110) mediates camp-independent PKA activation
AU - Niu, Jiaxin
AU - Vaiskunaite, Rita
AU - Suzuki, Nobuchika
AU - Kozasa, Tohru
AU - Carr, Daniel W.
AU - Dulin, Nickolai
AU - Voyno-Yasenetskaya, Tatyana A.
N1 - Funding Information:
We thank Sarah Andrews for editing this manuscript. This work was supported by grants from the National Institutes of Health: GM56159 (T.V.-Y.), GM59427 (T.K.), and HD36408 (D.W.C.). J.N. was supported by predoctoral fellowship 0110205Z from the American Heart Association.
PY - 2001/10/30
Y1 - 2001/10/30
N2 - 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.
AB - 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.
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U2 - 10.1016/S0960-9822(01)00530-9
DO - 10.1016/S0960-9822(01)00530-9
M3 - Article
C2 - 11696326
AN - SCOPUS:0035975936
SN - 0960-9822
VL - 11
SP - 1686
EP - 1690
JO - Current Biology
JF - Current Biology
IS - 21
ER -