Abstract
Calcineurin is a calcium-dependent protein phosphatase that plays a pivotal role in antigen-stimulated T cell activation. The complexes formed between the immunosuppressants cyclosporin A and FK506 and their respective intracellular binding proteins (immunophilins) block T cell activation by binding to calcineurin. Recent studies have shown that the immunophilin-immunosuppressant complexes interact with the latch region of the calcineurin B subunit (Milan, D., Griffith, J., Su, M., Price, E. R., and McKeon, F. (1994) Cell 79, 437-447). Mutations in the B subunit-binding domain of the calcineurin A subunit result in a reduction of calcineurin activity that correlates with B binding affinity. Calcineurin A subunit mutants D348A, F350A, W352A, S353A, and E359A lost greater than 90% of their activity to activate the transcription factor NF kappa B in Jurkat T cells. Furthermore, calcineurin A subunit mutants of residues Thr351, Leu354, and Lys360 showed NF kappa B transactivation activity and phosphatase activity with increased resistance to FKBP12-FK506 but displayed no or minimal increase in resistance for cyclosporin A inhibition. Together, these results strongly suggest that the B subunit-binding domain is required for calcineu...Continue Reading
References
May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S K SwansonF Rusnak
Jan 1, 1992·Annual Review of Immunology·N H Sigal, F J Dumont
Jun 25, 1992·Nature·S J O'KeefeE A O'Neill
Jun 25, 1992·Nature·N A Clipstone, G R Crabtree
Aug 7, 1992·Cell·S L Schreiber
Apr 30, 1992·Nature·J JainA Rao
Sep 2, 1991·Cell·J LiuS L Schreiber
Aug 29, 1991·Nature·W M FlanaganG R Crabtree
Aug 1, 1991·Transplantation·B D KahanS N Sehgal
Sep 18, 1990·Biochemistry·J A Wells
Sep 18, 1990·Biochemistry·U FinkeleD Oesterhelt
Jan 1, 1989·Immunology Today·A W Thomson
Feb 21, 1989·Biochemistry·M J Hubbard, C B Klee
Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D Guerini, C B Klee
Nov 1, 1989·DNA·D GueriniC B Klee
Dec 22, 1989·Science·E A EmmelG R Crabtree
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R L KincaidB M Martin
Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·T A Kunkel
Nov 1, 1984·Annals of Internal Medicine·D J CohenT B Strom
Nov 4, 1994·Cell·D MilanF McKeon
Jan 6, 1995·The Journal of Biological Chemistry·Y WatanabeT R Soderling
Jun 7, 1994·Biochemistry·P M Stemmer, C B Klee
Jul 28, 1993·Biochimica Et Biophysica Acta·T Muramatsu, R L Kincaid
Citations
Sep 1, 1996·Protein Science : a Publication of the Protein Society·J FejzoJ M Moore
Apr 14, 2005·Transplant International : Official Journal of the European Society for Organ Transplantation·Tudor BîrsanRandall E Morris
Mar 12, 1999·Gene·Z H Gao, G Zhong
Dec 31, 1997·Mutation Research·X Wu, M R Lieber
Aug 1, 1996·Current Opinion in Biotechnology·J E VillafrancaH E Parge
Mar 17, 2001·Molecular Microbiology·D S FoxJ Heitman
Feb 16, 2002·The EMBO Journal·M Cristina CruzJoseph Heitman
Aug 10, 2000·Transplantation·L Kung, P F Halloran
Feb 27, 2003·Antimicrobial Agents and Chemotherapy·Chiatogu OnyewuJoseph Heitman
Jan 19, 1999·Annual Review of Microbiology·D DiMaioO Klein
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·D J Stuehr
Feb 5, 2002·Annual Review of Physiology·Yoshiro Saimi, Ching Kung
Sep 23, 2009·Blood·Jennifer BrewinMartin Pule
Jul 31, 2012·PloS One·Karin HarrenBettina Tudzynski
Jul 24, 2002·European Journal of Biochemistry·Brian A PerrinoLucie H Clapp
Jul 5, 2005·Expert Opinion on Investigational Drugs·D Kletsas, A G Papavassiliou
Feb 13, 2016·FEBS Letters·Praveen R JuvvadiWilliam J Steinbach
Aug 31, 2006·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·John N CurranDavid Bouchier-Hayes
Aug 21, 2007·Biochemical and Biophysical Research Communications·Hailong WangQun Wei
Jan 12, 2013·European Journal of Pharmacology·Debbi MacMillan
Dec 17, 2014·Scientific Reports·Qi YuanGuangju Ji
Apr 7, 1998·The Journal of Trauma·T MatsudaM Ogawa
Jan 26, 2020·Microorganisms·Sofia Costa-de-Oliveira, Acácio G Rodrigues
Dec 14, 1999·The Journal of Biological Chemistry·X LinD L Barber
Dec 19, 2013·G3 : Genes - Genomes - Genetics·Arit GhoshKatherine A Borkovich
Jun 5, 1998·The Journal of Biological Chemistry·C B KleeX Wang
Nov 10, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mansi SaxenaAshok Kumar
May 8, 2018·Genetics·Sean ConnollyTami J Kingsbury
Mar 20, 2008·Biochemistry·Hailong WangQun Wei
Nov 10, 2005·Journal of Cell Science·Debbi MacMillanJohn G McCarron