- Peptide (C)RGAKRSRPSKLTED, corresponding to amino acid residues 128-141 of rat AKAP5 (Accession P24587). Intracellular.
- Western blot analysis of rat brain membranes (lanes 1 and 5), mouse brain membranes (lanes 2 and 6), rat dorsal root ganglion lysates (lanes 3 and 7) and mouse lung lysates (lanes 4 and 8):1-4. Anti-AKAP150 Antibody (#APZ-031), (1:200).
5-8. Anti-AKAP150 Antibody, preincubated with AKAP150 Blocking Peptide (#BLP-PZ031).
- Schwartz, J.H. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 13482.
- Feliciello, A. et al. (2001) J. Mol. Biol. 308, 99.
- Adler, E.M. (2014) J. Gen. Physiol. 143, 313.
- Esseltine, J.L. and Scott, J.D. (2013) Trends Pharmacol. Sci. 34, 648.
- Ting, J.T. et al. (2012) Annu. Rev. Neurosci. 35, 49.
- Nieves-Cintron, M. et al. (2016) Cell. Signal. 28, 733.
A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins that bind to the regulatory unit of Protein Kinase A (PKA) to discrete locations within the cell1. AKAPs include two conserved structural modules: a targeting domain that serves as a scaffold and membrane anchor that consists of two NH2-terminal structural modules that are highly conserved among mammalian homologues. They also have a tethering domain that interacts with PKA regulatory subunits which consists of a short amphipathic helix. Alternative splicing can shuffle targeting and tethering domains to generate a variety of AKAPs with different targeting specificity. Although AKAPs have been identified on the basis of their interaction with PKA, they also bind other signaling molecules, mainly phosphatases and kinases that regulate AKAP targeting and activate other signal transduction pathways2.
Some types of AKAPs interact with CaV1.1 and CaV1.2. These voltage-gated calcium channels are phosphorylated by PKA after β-adrenergic activation. This phosphorylation is enabled by the binding of AKAP150 to the distal C-terminal of CaV1.1 and CaV1.2. Binding of different AKAPs that interact with distinct signaling partners to the calcium channel intracellular C-terminal domain may act to fine-tune channel activity and downstream calcium-mediated processes3.
A single subtype of neuronal AKAP is expressed widely in the brain and is highly conserved in mouse (150 kDA), bovine (75 kDA) and human (79 kDA). APAK150 targets PKAII to the postsynaptic cytoskeleton and perikarya of neurons. It is expressed in Purkinje cells and in olfactory bulb neurons, basal ganglia, cerebral cortex and other forebrain areas. AKAP150 is concentrated in primary branches of dendrites in association with microtubules. The localization of PKAIIβ in brain overlaps with that of AKAP150, suggesting that AKAP150 is the relevant PKAIIβ anchor protein in the brain2.
Inhibition of either AKAP150 or TRPV1 binding sites causes an abolishment of PKC-dependent TRPV1 sensitization to capsaicin stimuli thus making the AKAP150-TRPV1 interaction a viable target for novel analgesics4.
AKAP150 interacts with another group of scaffolding proteins known as the SAP90/PSD95-associated protein family. AKAP150 interacts directly with the SH3 and GK domains of PSD95 and SAP97. These proteins have specific roles in synaptic localization of NMDARs and AMPARs respectively5.
Post myocardial infarction, AKAP150-mediated targeting of calcineurin to sarcolemmal micro-domains in ventricular myocytes contributes to the local and acute gene remodeling events that lead to the down-regulation of KV currents6.
Species reactivity key:
Anti-AKAP150 Antibody (#APZ-031) is a highly specific antibody directed against an epitope of the rat protein. The antibody can be used in western blot analysis. It has been designed to recognize AKAP150 from mouse and rat samples. The antibody is unlikely to recognize AKAP5 from human samples.