A-kinase-anchoring proteins

Open Access
Publisher Website
Google Scholar
Abstract
Doi:10.1242/jcs.02416 Highly organized molecular complexes determine the precise location and timing of the signal transduction events that occur downstream of cell surface receptor activation (Pawson and Nash, 2003). One set of scaffolding molecules that organize such complexes is a family of proteins known as A-kinase-anchoring proteins (AKAPs). AKAPs provide a framework for the coordination of phosphorylation and dephosphorylation events by sequestering enzymes such as protein kinases and phosphatases with appropriate substrates. AKAPs also bring together signal transduction and signal termination molecules in a convergence of signaling pathways. Indeed, the dynamic assembly of these AKAP complexes represents a paradigm of higher-order signal organization (Wong and Scott, 2004). AKAPs were first identified as a family of structurally diverse but functionally related proteins that share the capacity to bind protein kinase A (PKA) (Lohmann et al., 1984; Theurkauf and Vallee, 1982). The hydrophobic face of a conserved amphipathic helix within AKAPs anchors PKA through interaction with an N-terminal four-helix bundle in the regulatory subunit (R) dimer (Carr et al., 1991; Newlon et al., 1999). In addition, a distinct region of the AKAP contains a targeting sequence that serves to tether the complex to a specific subcellular compartment (Colledge and Scott, 1999). Anchoring of the kinase facilitates localized activation of the PKA catalytic subunit (C) following elevation of the second messenger cyclic AMP (cAMP). Importantly, it has been shown by many labs that, in addition to directing the action of PKA, AKAPs engage other signaling molecule