Historical Background
The serine-/threonine-specific protein phosphatase calcineurin is conserved from yeast to man and was first detected in bovine brain extracts by Wang and Desai and independently by Watterson and Vanaman in 1976 (Wang and Desai 1976; Watterson and Vanaman 1976). Klee and Krinks were the first to purify calcineurin in 1978 (Klee and Krinks 1978), and Klee also coined the name “calcineurin,” since the protein was extracted from brain tissue and it could bind Ca2+ (Klee et al. 1979). However, the function of calcineurin was not known at this time. It was assumed that calcineurin might be a regulatory subunit of the phosphodiesterase, as it could inhibit phosphodiesterase activity. In the early 1980s, the real function as a phosphatase was demonstrated. Stewart et al. found that the protein phosphatase 2B isolated from rabbit skeletal muscle was identical to the previously identified calcineurin...
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Adler A, Park YD, Larsen P, Nagarajan V, Wollenberg K, Qiu J, et al. A novel specificity protein 1 (SP1)-like gene regulating protein kinase C-1 (Pkc1)-dependent cell wall integrity and virulence factors in Cryptococcus neoformans. J Biol Chem. 2011;286(23):20977–90.
Aichem A, Mutzel R. Unconventional mRNA processing in the expression of two calcineurin B isoforms in Dictyostelium. J Mol Biol. 2001;308(5):873–82.
Flanagan WM, Corthesy B, Bram RJ, Crabtree GR. Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 1991;352(6338):803–7.
Goldman A, Roy J, Bodenmiller B, Wanka S, Landry CR, Aebersold R, et al. The calcineurin signaling network evolves via conserved kinase-phosphatase modules that transcend substrate identity. Mol Cell. 2014;55(3):422–35.
Juvvadi PR, Gehrke C, Fortwendel JR, Lamoth F, Soderblom EJ, Cook EC, et al. Phosphorylation of Calcineurin at a novel serine-proline rich region orchestrates hyphal growth and virulence in Aspergillus fumigatus. PLoS Pathog. 2013;9(8):e1003564.
Klee CB, Krinks MH. Purification of cyclic 3′,5′-nucleotide phosphodiesterase inhibitory protein by affinity chromatography on activator protein coupled to Sepharose. Biochemistry. 1978;17(1):120–6.
Klee CB, Crouch TH, Krinks MH. Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc Natl Acad Sci U S A. 1979;76(12):6270–3.
Li H, Rao A, Hogan PG. Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol. 2011;21(2):91–103.
Li X, Wilmanns M, Thornton J, Kohn M. Elucidating human phosphatase-substrate networks. Sci Signal. 2013;6(275):rs10.
Liu J, Farmer Jr JD, Lane WS, Friedman J, Weissman I, Schreiber SL. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991;66(4):807–15.
Miyata H, Satouh Y, Mashiko D, Muto M, Nozawa K, Shiba K, et al. Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive. Science. 2015;350(6259):442–5.
Müller MR, Rao A. NFAT, immunity and cancer: a transcription factor comes of age. Nat Rev Immunol. 2010;10(9):645–56.
Namgaladze D, Hofer HW, Ullrich V. Redox control of calcineurin by targeting the binuclear Fe(2+)-Zn(2+) center at the enzyme active site. J Biol Chem. 2002;277(8):5962–9.
Rothermel BA, Vega RB, Williams RS. The role of modulatory calcineurin-interacting proteins in calcineurin signaling. Trends Cardiovasc Med. 2003;13(1):15–21.
Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev. 2000;80(4):1483–521.
Stathopoulos AM, Cyert MS. Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast. Genes Dev. 1997;11(24):3432–44.
Stewart AA, Ingebritsen TS, Manalan A, Klee CB, Cohen P. Discovery of a Ca2+− and calmodulin-dependent protein phosphatase: probable identity with calcineurin (CaM-BP80). FEBS Lett. 1982;137(1):80–4.
Thewes S. Calcineurin-Crz1 signaling in lower eukaryotes. Eukaryot Cell. 2014a;13(6):694–705.
Thewes S. The role of calcineurin during development: parallels and differences between higher and lower eukaryotes. Cell News. 2014b;40(4):10–6.
Wang JH, Desai R. A brain protein and its effect on the Ca2+−and protein modulator-activated cyclic nucleotide phosphodiesterase. Biochem Biophys Res Commun. 1976;72(3):926–32.
Watterson DM, Vanaman TC. Affinity chromatography purification of a cyclic nucleotide phosphodiesterase using immobilized modulator protein, a troponin C-like protein from brain. Biochem Biophys Res Commun. 1976;73(1):40–6.
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Thewes, S. (2018). Calcineurin. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101959
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101959
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