CAMK4 explained

Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.^[1]

The product of this gene belongs to the serine/threonine protein kinase cluster, and to the Ca²⁺/calmodulin-dependent protein kinase (CAMK) group. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons, and male germ cells.^[2]

Further reading

• Bredt DS, Ferris CD, Snyder SH . Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites . J. Biol. Chem. . 267 . 16 . 10976–81 . 1992 . 10.1016/S0021-9258(19)49862-1 . 1375933 . free .
• Jensen KF, Ohmstede CA, Fisher RS, Sahyoun N . Nuclear and axonal localization of Ca²⁺/calmodulin-dependent protein kinase type Gr in rat cerebellar cortex . Proc. Natl. Acad. Sci. U.S.A. . 88 . 7 . 2850–3 . 1991 . 2011593 . 10.1073/pnas.88.7.2850 . 51337 . 1991PNAS...88.2850J . free .
• Selbert MA, Anderson KA, Huang QH . Phosphorylation and activation of Ca²⁺-calmodulin-dependent protein kinase IV by Ca²⁺-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine 196 is essential for activation . J. Biol. Chem. . 270 . 29 . 17616–21 . 1995 . 7615569 . 10.1074/jbc.270.29.17616. etal. free .
• Kitani T, Okuno S, Fujisawa H . cDNA cloning and expression of human calmodulin-dependent protein kinase IV . J. Biochem. . 115 . 4 . 637–40 . 1994 . 8089075 . 10.1093/oxfordjournals.jbchem.a124387.
• Mosialos G, Hanissian SH, Jawahar S . A Ca²⁺/calmodulin-dependent protein kinase, CaM kinase-Gr, expressed after transformation of primary human B lymphocytes by Epstein-Barr virus (EBV) is induced by the EBV oncogene LMP1 . J. Virol. . 68 . 3 . 1697–705 . 1994 . 8107230 . 10.1128/JVI.68.3.1697-1705.1994. 236629 . etal.
• Bland MM, Monroe RS, Ohmstede CA . The cDNA sequence and characterization of the Ca²⁺/calmodulin-dependent protein kinase-Gr from human brain and thymus . Gene . 142 . 2 . 191–7 . 1994 . 8194751 . 10.1016/0378-1119(94)90260-7 .
• Tokumitsu H, Soderling TR . Requirements for calcium and calmodulin in the calmodulin kinase activation cascade . J. Biol. Chem. . 271 . 10 . 5617–22 . 1996 . 8621423 . 10.1074/jbc.271.10.5617 . free .
• Chatila T, Anderson KA, Ho N, Means AR . A unique phosphorylation-dependent mechanism for the activation of Ca²⁺/calmodulin-dependent protein kinase type IV/GR . J. Biol. Chem. . 271 . 35 . 21542–8 . 1996 . 8702940 . 10.1074/jbc.271.35.21542 . free .
• Melander Gradin H, Marklund U, Larsson N . Regulation of microtubule dynamics by Ca²⁺/calmodulin-dependent kinase IV/Gr-dependent phosphorylation of oncoprotein 18 . Mol. Cell. Biol. . 17 . 6 . 3459–67 . 1997 . 9154845 . 10.1128/mcb.17.6.3459. 232199 . etal.
• Matsushita M, Nairn AC . Characterization of the mechanism of regulation of Ca²⁺/ calmodulin-dependent protein kinase I by calmodulin and by Ca²⁺/calmodulin-dependent protein kinase kinase . J. Biol. Chem. . 273 . 34 . 21473–81 . 1998 . 9705275 . 10.1074/jbc.273.34.21473 . free .
• Anderson KA, Means RL, Huang QH . Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca²⁺/calmodulin-dependent protein kinase kinase beta . J. Biol. Chem. . 273 . 48 . 31880–9 . 1998 . 9822657 . 10.1074/jbc.273.48.31880 . etal. free .
• Hayashi Y, Nishio M, Naito Y . Regulation of neuronal nitric-oxide synthase by calmodulin kinases . J. Biol. Chem. . 274 . 29 . 20597–602 . 1999 . 10400690 . 10.1074/jbc.274.29.20597 . etal. free .
• Blaeser F, Ho N, Prywes R, Chatila TA . Ca²⁺-dependent gene expression mediated by MEF2 transcription factors . J. Biol. Chem. . 275 . 1 . 197–209 . 2000 . 10617605 . 10.1074/jbc.275.1.197 . free .
• Moreno CS, Park S, Nelson K . WD40 repeat proteins striatin and S/G(2) nuclear autoantigen are members of a novel family of calmodulin-binding proteins that associate with protein phosphatase 2A . J. Biol. Chem. . 275 . 8 . 5257–63 . 2000 . 10681496 . 10.1074/jbc.275.8.5257 . 3505218. etal. free .
• Komeima K, Hayashi Y, Naito Y, Watanabe Y . Inhibition of neuronal nitric-oxide synthase by calcium/ calmodulin-dependent protein kinase IIalpha through Ser847 phosphorylation in NG108-15 neuronal cells . J. Biol. Chem. . 275 . 36 . 28139–43 . 2000 . 10874031 . 10.1074/jbc.M003198200 . free .
• Wu JY, Ribar TJ, Cummings DE . Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking Camk4 . Nat. Genet. . 25 . 4 . 448–52 . 2000 . 10932193 . 10.1038/78153 . 10803791 . etal.
• Jang MK, Goo YH, Sohn YC . Ca²⁺/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit . J. Biol. Chem. . 276 . 23 . 20005–10 . 2001 . 11274168 . 10.1074/jbc.M010211200 . etal. free .
• Hsu LS, Chen GD, Lee LS . Human Ca²⁺/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity . J. Biol. Chem. . 276 . 33 . 31113–23 . 2001 . 11395482 . 10.1074/jbc.M011720200 . etal. free .
• Zhao X, Ito A, Kane CD . The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking . J. Biol. Chem. . 276 . 37 . 35042–8 . 2001 . 11470791 . 10.1074/jbc.M105086200 . etal. free .
• Loss of the Ca²⁺/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine. PNAS. Ainhoa Bilbaoa. Jan Rodriguez Parkitnab. David Engblomb. Stéphanie Perreau-Lenza. Carles Sanchis-Seguraa. Miriam Schneidera. Witold Konopkab. Magdalena Westphalb. Gerome Breenc. Sylvane Desrivieresc. Matthias Klugmannd. Camila Guindalinie. Homero Valladag. Ronaldo Laranjeirae. Fernando Rodriguez de Fonsecah. Gunter Schumannc. Günther Schützb. Rainer Spanagela. amp. 19001277. 10.1073/pnas.0803959105. 2008. 105. 45. 17549–54. 2582267. Proceedings of the National Academy of Sciences of the United States of America. 2008PNAS..10517549B . free.
• Feliciano DM, Edelman AM . Repression of Ca²⁺/calmodulin-dependent protein kinase IV signaling accelerates retinoic acid-induced differentiation of human neuroblastoma cells.. J. Biol. Chem. . 284 . 39 . 26466–81 . 2009 . 19633294 . 10.1074/jbc.M109.027680 . 2785335. free.

Notes and References

1. Sikela JM, Law ML, Kao FT, Hartz JA, Wei Q, Hahn WE . Chromosomal localization of the human gene for brain Ca²⁺/calmodulin-dependent protein kinase type IV . Genomics . 4 . 1 . 21–7 . Mar 1989 . 2536634 . 10.1016/0888-7543(89)90309-1 .
2. Web site: Entrez Gene: CAMK4 calcium/calmodulin-dependent protein kinase IV.