AKAP

signaling com towards the next ge, U Reviewtenets of AKAP signaling: specificity, sensitivity, localiza-tion, and temporal control. Recently, investigators are shifting their attention from cells in culture towards in vivo models in order to understand how anchored signaling pathways are per-turbed during disease. This comes at a time when approx-imately 50 % of marketed pharmaceuticals target G protein-coupled receptors (GPCRs) and increasing numbers of kinase inhibitor drugs are entering the quired for binding to PP2B was originally mapped more than 10 years ago, recent work has identified a specific sequence within this region, which bears striking resem-blance to the PIxIxIT motif in NFAT [11,12]. The authors showed that this region was responsible for the AKAP79/ 150-mediated activation of NFAT by PP2B [11,12]. In rat hippocampal neurons NFAT signaling is initiated via AKAP79/150-anchored Cav1.2-mediated increases in in-tracellular Ca2+, PP2B activation, and NFAT dephosphor-ylation, allowing NFAT translocation to the nucleus where it regulates gene transcription. Additionally, AKAP150-dependent nuclear translocation of NFAT regulates gene expression of KCNQ2 and KCNQ3 potassium channels and is abolished in AKAP150 null mice [13]. Activation of AKAP-anchored PP2B involves local Ca2+ influx through the L-type voltage-gated Ca2+ channel, Cav1.2. However, negative feedback regulation of the chan-nel also appears to be modulated by PP2B as deletion of the 0165-6147/ $ – see front matte