Structural highlights
3ll8 is a 5 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Gene: | PPP3CA, CALNA, CNA (HUMAN), PPP3R1, CNA2, CNB (HUMAN) |
| Activity: | Phosphoprotein phosphatase, with EC number 3.1.3.16 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[AKAP5_HUMAN] May anchor the PKA protein to cytoskeletal and/or organelle-associated proteins, targeting the signal carried by cAMP to specific intracellular effectors. Association with to the beta2-adrenergic receptor (beta2-AR) not only regulates beta2-AR signaling pathway, but also the activation by PKA by switching off the beta2-AR signaling cascade. [CANB1_HUMAN] Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity. [PP2BA_HUMAN] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.[1] [2]
Publication Abstract from PubMed
In hippocampal neurons, the scaffold protein AKAP79 recruits the phosphatase calcineurin to L-type Ca(2+) channels and couples Ca(2+) influx to activation of calcineurin and of its substrate, the transcription factor NFAT. Here we show that an IAIIIT anchoring site in human AKAP79 binds the same surface of calcineurin as the PxIxIT recognition peptide of NFAT, albeit more strongly. A modest decrease in calcineurin-AKAP affinity due to an altered anchoring sequence is compatible with NFAT activation, whereas a further decrease impairs activation. Counterintuitively, increasing calcineurin-AKAP affinity increases recruitment of calcineurin to the scaffold but impairs NFAT activation; this is probably due to both slower release of active calcineurin from the scaffold and sequestration of active calcineurin by 'decoy' AKAP sites. We propose that calcineurin-AKAP79 scaffolding promotes NFAT signaling by balancing strong recruitment of calcineurin with its efficient release to communicate with NFAT.
Balanced interactions of calcineurin with AKAP79 regulate Ca(2+)-calcineurin-NFAT signaling.,Li H, Pink MD, Murphy JG, Stein A, Dell'acqua ML, Hogan PG Nat Struct Mol Biol. 2012 Feb 19;19(3):337-45. doi: 10.1038/nsmb.2238. PMID:22343722[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang Y, Shibasaki F, Mizuno K. Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot via calcineurin. J Biol Chem. 2005 Apr 1;280(13):12683-9. Epub 2005 Jan 24. PMID:15671020 doi:M411494200
- ↑ Cereghetti GM, Stangherlin A, Martins de Brito O, Chang CR, Blackstone C, Bernardi P, Scorrano L. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15803-8. doi:, 10.1073/pnas.0808249105. Epub 2008 Oct 6. PMID:18838687 doi:10.1073/pnas.0808249105
- ↑ Li H, Pink MD, Murphy JG, Stein A, Dell'acqua ML, Hogan PG. Balanced interactions of calcineurin with AKAP79 regulate Ca(2+)-calcineurin-NFAT signaling. Nat Struct Mol Biol. 2012 Feb 19;19(3):337-45. doi: 10.1038/nsmb.2238. PMID:22343722 doi:10.1038/nsmb.2238
