Signaling AKAPs

AKAPs are a diverse family of about 75 scaffolding proteins. They are defined by the presence of a structurally conserved protein kinase A (PKA)-binding domain. AKAPs tether PKA and other signalling proteins to cellular compartments and thereby limit and integrate cellular signalling processes at specific sites. This compartmentalization of signalling by AKAPs contributes to the specificity of a cellular response to a given external stimulus (e.g. a particular hormone or neurotransmitter). 

The tethering of PKA through AKAPs by itself is not sufficient to compartmentalize and control a cAMP/ PKA-dependent pathway. Cyclic AMP readily diffuses throughout the cell. Therefore, discrete cAMP/PKA signalling compartments are only conceivable if this diffusion is limited. Phosphodiesterases (PDE) establish gradients of cAMP by local hydrolysis of the... 

AKAPs Optimise the Limited Repertoire of Cellnlar Signalling Proteins... 

Wong W, Scott JD (2004) AKAP signalling complexes focal points in space and time. Nat Rev Mol Cell Biol 5 959-970... 

Michel, J.J.C. Scott, J.D. (2002) AKAP mediated signal transduction. Annu. Rev. Pharmacol Toxicol. 42, 235-257. 

Now covers the roles of membrane rafts and caveolae in signaling pathways, including the activities of AKAPs (A Kinase Anchoring Proteins) and other scaffold proteins... 

Maynard TM, Sikich L, Lieberman JA, LaMantia A-S. 2001. Neural development, cell-signaling, and the two-hit hypothesis of schizophrenia. Schizophr Bull 27 457-476. McConnachie G, Langeberg LK, Scott JD. 2006. AKAP signaling complexes Getting to the heart of the matter. Trends Mol Med 12 317-323. 

Glantz SB, Amat JA, Rubin CS (1992) cAMP signaling in neurons patterns of neuronal expression and intracellular localization for a novel protein, AKAP 150, that anchors the regulatory subunit of cAMP-dependent protein kinase II beta. Mol Biol Cell 3 1215-1228. 

Fig. 7.21 Model of a signaling complex organized at the membrane of a target organelle by AKAPs. A schematic representation of a multiprotein complex formed by a prototypic AKAP, protein kinase A and two other effector proteins, protein phosphatase (PPase) and protein kinase C (PKC), both activated by calcium. DAC diacylglycerol.

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