Tasken, Kjetil, and Einar Martin Aandahl. Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A. Physiol Rev 84: 137–167, 2004; 10.1152/physrev.00021.2003.—More than 20% of the ...

https://www.physiology.org/doi/pdf/10.1152/physrev.00021.2003

Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A

A large number of hormones, neurotransmitters and other signal substances utilize adenosine 3',5' cyclic monophosphate (cAMP) as an intracellular second messenger. Cyclic AMP regulates a number of different cellular processes such as cell growth and differentiation, ion channel conductivity, synaptic release of neurotransmitters, and gene transcription. The principle intracellular target for cAMP in mammalian cells is the cAMP-dependent protein kinase (PKA). The fact that this broad specificity protein kinase mediates a number of discrete physiological responses following cAMP-engagement, has raised the question of how specificity is maintained in the cAMP/PKA system. Here we will describe features of this signaling pathway that may contribute to explain how differential effects of cAMP may be contributed to features of the PKA signaling pathway.

https://www.bioscience.org/1997/v2/d/skalhegg/skalhegg.pdf

Specificity in the cAMP/PKA signaling pathway. differential expression, regulation, and subcellular localization of subunits of PKA.

Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in the centrosomal area.

Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding.

A combination of protein kinase A type II (RII) overlay screening, database searches and PCR was used to identify a centrosomal A-kinase anchoring protein. A cDNA with an 11.7 kb open reading frame was characterized and found to correspond to 50 exons of genomic sequence on human chromosome 7q21-22. This cDNA clone encoded a 3908 amino acid protein of 453 kDa, that was designated AKAP450 (DDBJ/EMBL/GenBank accession No. AJ131693). Sequence comparison demonstrated that the open reading frame contained a previously characterized cDNA encoding Yotiao, as well as the human homologue of AKAP120. Numerous coiled-coil structures were predicted from AKAP450, and weak homology to pericentrin, giantin and other structural proteins was observed. A putative RII-binding site was identified involving amino acid 2556 of AKAP450 by mutation analysis combined with RII overlay and an amphipatic helix was predicted in this region. Immunoprecipitation of RII from RIPA-buffer extracts of HeLa cells demonstrated co-precipitation of AKAP450. By immunofluorecent labeling with specific antibodies it was demonstrated that AKAP450 localized to centrosomes. Furthermore, AKAP450 was shown to co-purify in centrosomal preparations. The observation of two mRNAs and several splice products suggests additional functions for the AKAP450 gene.

/pdf/cloning-and-characterization-of-a-cdna-encoding-an-a-kinase-cvvgocyovb.pdf

Vince Coghlan

Papers

Molecular cloning, chromosomal localization, and cell cycle-dependent subcellular distribution of the A-kinase anchoring protein, AKAP95.