心力衰竭时,交感神经系统激活,儿茶酚胺激活β受体(β-AR)通过Gs蛋白-腺苷酸环化酶-环磷酸腺苷-蛋白激酶A(Gs-AC-c AMPPKA)信号通路增加心输出量,这在短期内有益,但持续激活β受体最终会导致心脏收缩力降低.在这一病理过程中,A型激酶锚定蛋白(AKAP)起着重要的作用,AKAP通过将PKA锚定在特定的亚细胞区域来调节...
PKA is retained within distinct subcellular environments by the association of its regulatory type II (RII) subunits with A-kinase anchoring proteins (AKAPs). Conventional reagents that universally disrupt PKA anchoring are patterned after a conserved AKAP motif. We introduce a phage selection ...
However, basal PKA activity could also play important regulatory roles in the context of AKAP-anchored complexes, where PKA catalytic subunits have intimate access to substrate proteins, even in the absence of cAMP stimulation, but surprisingly, the role of AKAP79/150-anchored PKA in controlling ...
The cAMP-dependent protein kinase (PKA) is retained within distinct subcellular environments by the association of its type-II (RII) regulatory subunits with A-Kinase Anchoring Proteins (AKAPs). Conventional reagents that universally disrupt PKA anchoring are patterned after a conserved AKAP motif. We...
PKA regulatory subunitThe main function of the A kinase‐anchoring proteins (AKAP s) is to target the cyclic AMP‐dependent protein kinase A (PKA ) to its cellular substrates through the interaction with its regulatory subunits. Besides anchoring of PKA , AKAP 8 participates in regulating the ...
Klussmann, Dr. EnnoRosenthal, WalterFrank, ChristianGenieser, Hans-gottfriedZimmermann, BastianSzaszak, Dr. MartaEPEP2098226A1 * Mar 6, 2008 Sep 9, 2009 Forschungsverbund Berlin e.V. AKAP-PKA interaction inhibitors for use in the treatment of heart diseases...
A Kinase Anchoring Proteins (AKAPs) serve as scaffold proteins that target the PKA isoforms to distinct parts of the cell. The hallmark motif that defines an AKAP is an amphipathic helix that docks with high affinity (2–7 nM) onto the N-terminal helical dimerization/docking domain of the ...
Highly functionalized terpyridines as competitive inhibitors of AKAP-PKA interactions. Angew. Chem. Int. Ed. Engl. 2013, 52, 12187-12191.Schafer G, Milic J, Eldahshan A et al (2013) Highly functionalized terpyridines as competi- tive inhibitors of AKAP-PKA interactions. Angew Chem Int Ed ...
These engineered proteins represent a new class of reagents that can be used to dissect the contributions of different AKAP-targeted pools of PKA. Molecular modeling and high-throughput sequencing analyses revealed the molecular basis of AKAP-selective interactions and shed new light on native RII-...
PKA activation of Kv currents remained following disruption of PKA-AKAP interactions.Jennifer L. BrignellMatthew D. PerryCarl P. NelsonJonathon M. WilletsR. A. John ChallissNoel W. Davies