Dr. Eileen Kennedy, Assistant Professor, has published a paper in Biochemical Journal: “AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA”. Dr. Kennedy was also invited to speak at the 13th Annual Biochemistry Retreat for Universitat Kassel, held in Wesendorf, Germany, January 20-23, 2016. The title of her presentation was “Targeting regulation and allosteric activation of kinases.”
“AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA” authors were
Abstract: A-kinase anchoring proteins (AKAPs) interact with the dimerization/docking (D/D) domains of regulatory subunits of the ubiquitous protein kinase A (PKA). AKAPs tether PKA to defined cellular compartments establishing distinct pools to increase the specificity of PKA signalling. Here, we elucidated the structure of an extended PKA-binding domain of AKAP18β bound to the D/D domain of the regulatory RIIα subunits of PKA. We identified three hydrophilic anchor points in AKAP18β outside the core PKA-binding domain, which mediate contacts with the D/D domain. Such anchor points are conserved within AKAPs that bind regulatory RII subunits of PKA. We derived a different set of anchor points in AKAPs binding regulatory RI subunits of PKA. <em>In vitro</em> and cell-based experiments confirm the relevance of these sites for the interaction of RII subunits with AKAP18 and of RI subunits with the RI-specific smAKAP. Thus we report a novel mechanism governing interactions of AKAPs with PKA. The sequence specificity of each AKAP around the anchor points and the requirement of these points for the tight binding of PKA allow the development of selective inhibitors to unequivocally ascribe cellular functions to the AKAP18-PKA and other AKAP-PKA interactions.