A-Kinase Anchoring Protein Lbc Coordinates a p38 Activating Signaling Complex Controlling Compensatory Cardiac Hypertrophy

López, Irene Pérez; Cariolato, Luca; Maric, Darko; Gillet, Ludovic; Abriel, Hugues; Diviani, Dario

doi:10.1128/mcb.00913-13

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2016

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“…In addition, AKAPs bind GPCRs [11], ACs [12,13], exchange proteins directly activated by cAMP (Epac) [14], phosphodiesterases (PDEs) [15,16], protein kinases (e.g. protein kinases C, D and N) [17], protein phosphatases such as PP1 [18] and PP2B (calcineurin) [19,20] and ion channels and pumps (e.g. L--type Ca 2+ channels, Na + --Ca 2+…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease

Deák¹,

Klussmann

2016

CDT

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A--kinase anchoring proteins (AKAPs) control the localization of cAMP--dependent protein kinase A (PKA) by tethering PKA to distinct cellular compartments. Through additional direct protein--protein interactions with PKA substrates and other signaling molecules they form multi--protein complexes. Thereby, AKAPs regulate the access of PKA to its substrates in a temporal and spatial manner as well as the local crosstalk of cAMP/PKA with other signaling pathways.Due to the increasing information on their molecular functioning and three--dimensional structures, and their emerging roles in the development of diseases, AKAPs move into the focus as potential drug targets. In particular, targeting AKAP--dependent protein--protein interactions for interference with local signal processing inside cells potentially allows for the development of therapeutics with high selectivity and fewer side effects.4

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