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

Heterotrimeric G proteins [1] and protein kinase A (PKA) are two important transmitters that transfer signals from a wide variety of cell surface rece ptors 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 subsequ ent activation of a catalytic subunit of PKA (cPKA). Here, we report a nove l mechanism of PKA stimulation that does not require CAMP. Using yeast two- hybrid screening, we found that the a subunit of G13 protein interacted wit h a member of the PKA-anchoring protein family, AKAP110. Using in vitro bin ding and coimmunoprecipitation assays, we have shown that only activated G alpha 13 binds to AKAP110, suggesting a potential role for AKAP110 as a Get subunit effector protein. Importantly, G alpha 13, AKAP110, rPKA, and cPKA can form a complex, as shown by coimmunoprecipitation. By characterizing t he functional significance of the G alpha 13-AKAP110 interaction, we have f ound that G alpha 13 induced release of the cPKA from the AKAP110-rPKA comp lex, resulting in a cAMP-independent PKA activation. Finally, AKAP110 signi ficantly potentiated G alpha 13-induced activation of PKA. Thus, AKAP110 pr ovides a link between heterotrimeric G proteins and cAMP-independent activa tion of PKA.