The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Csnk1a1  -  casein kinase 1, alpha 1

Rattus norvegicus

Synonyms: CK1, CKI-alpha, Casein kinase I isoform alpha
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Csnk1a1

  • All three CK1 gamma isoforms were expressed as active enzymes in Escherichia coli and partially purified [1].
  • Regulation of ornithine decarboxylase mRNA by phorbol esters and insulin in normal and C-kinase-deficient rat hepatoma cells [2].
  • It is suspected that the suppression of insulin release from pancreatic islets by Vacor may contribute to the pathogenesis of Vacor-induced diabetes mellitus and that this suppression might not be related to cAMP and C-kinase [3].
  • 1. Two kinds of C-kinase inhibitors were indicated to be present in mastocytoma cells [4].
  • Phorbol ester treatment induced 5- to 10-fold increases in phosphorylation of the myristoylated alanine-rich C kinase substrate protein in muscle, whereas insulin and hypoxia had negligible effects [5].

High impact information on Csnk1a1

  • Thus, activation of the Ca++-dependent enzyme, C kinase, modulates EGF receptor affinity, possibly via altered receptor phosphorylation [6].
  • Reconstitution of unresponsive membranes with purified C kinase alters phosphorylation of the EGF receptor and restores the inhibitory effect of phorbol esters on 125I-EGF binding previously observed only in intact cells [6].
  • Here we examine how glutamate receptor interacting protein (GRIP, also known as AMPAR binding protein or ABP) and protein interacting with C-kinase-1 (PICK) regulate subunit trafficking and plasticity [7].
  • We investigated the role of MARCKS (myristoylated, alanine-rich C-kinase substrate) in dendrites of 3-week-old hippocampal cultures [8].
  • Both 12-O-tetradecanoyl phorbol 13-acetate and 1,25(OH)2D3 activated endogenous PKC, as assessed by inhibition of myristoylated alanine-rich C kinase substrate back-phosphorylation by exogenous PKC [9].

Biological context of Csnk1a1


Anatomical context of Csnk1a1

  • Several endogenous substrate proteins for C kinase ranging from 16 to 100 kDa were identified in pituitary cytosol [13].
  • However, the beta-catenin sequence downstream from Ser-45 is very similar to a sequence recognized by CK1 in nuclear factor for activated T cells 4 [15].
  • There is a strong correlation of beta-catenin mutations found in thyroid tumors with the motifs recognized by CK1 in this protein [15].
  • The idea that the inhibition of synaptosome K channels by diC8 resulted from activation of C kinase was supported by pharmacological evidence [16].
  • Using a partial cDNA fragment corresponding to an isoform termed CK1 gamma, three full-length rat testis cDNAs were cloned that defined three separate members of this subfamily [1].

Associations of Csnk1a1 with chemical compounds

  • This inhibition is mediated by activation of cAMP-dependent kinase as it is prevented by pretreatment with the A-kinase inhibitor, N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide (H8) but not by the C-kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) [17].
  • Pretreatment with either staurosporine, C-kinase inhibitor, or calmidazolium, a calmodulin inhibitor, partially prevented but, together, completely prevented the inhibitory effect of phenylephrine [18].
  • Carbachol and the C kinase activator 120-tetradecanoylphorbol-13-acetate also stimulated histamine release [19].
  • Hydrolysis of inositol phospholipids by receptor stimulation activates two separate signaling pathways, one leading to the activation of protein kinase C (C kinase) via formation of diacylglycerol [20].
  • The C-kinase inhibitors chlorpromazine and trifluoperazine inhibit the phorbol diester stimulated phosphorylation of site T3 in a dose-dependent manner [21].

Regulatory relationships of Csnk1a1


Other interactions of Csnk1a1


Analytical, diagnostic and therapeutic context of Csnk1a1

  • Cellular co-immunoprecipitation experiments and in vitro CK1 phosphorylation reactions indicate that CK1 interacted with and phosphorylated Cx43, initially on serine(s) 325, 328, or 330 [14].
  • Immunofluorescence experiments in the presence of CK1 inhibitor showed increases in Cx43 plasma membrane localization but not necessarily accumulation at cell-cell interfaces [14].
  • Microinjection of purified calcium phospholipid-dependent protein kinase (C-kinase) resulted in the rapid and transient induction of c-fos in quiescent rat embryo fibroblats [28].
  • Myristoylated alanine-rich C kinase substrate messenger RNA exhibited a robust increase in both neurons and non-neuronal cells in the facial motor nucleus beginning four days after axotomy, peaked at seven days (2.5-fold), and declined back to baseline levels by 40 days [26].
  • A broad area of C-kinase inhibitory activity was detected after DEAE-cellulose chromatography of 20,000 g supernatant of rat stomach homogenate [29].


  1. Casein kinase I gamma subfamily. Molecular cloning, expression, and characterization of three mammalian isoforms and complementation of defects in the Saccharomyces cerevisiae YCK genes. Zhai, L., Graves, P.R., Robinson, L.C., Italiano, M., Culbertson, M.R., Rowles, J., Cobb, M.H., DePaoli-Roach, A.A., Roach, P.J. J. Biol. Chem. (1995) [Pubmed]
  2. Regulation of ornithine decarboxylase mRNA by phorbol esters and insulin in normal and C-kinase-deficient rat hepatoma cells. Butler, A.P., Cohn, W.B., Mar, P.K., Montgomery, R.L. J. Cell. Physiol. (1991) [Pubmed]
  3. Vacor inhibits insulin release from islets in vitro. Taniguchi, H., Yamashiro, Y., Chung, M.Y., Hara, Y., Ishihara, K., Ejiri, K., Baba, S. J. Endocrinol. Invest. (1989) [Pubmed]
  4. Evidence for the presence of cytosolic inhibitors for phospholipid/Ca2+-dependent protein kinase in mastocytoma cell. Nagata, K., Nagao, S., Ishizuka, T., Nozawa, Y. Comp. Biochem. Physiol., B (1988) [Pubmed]
  5. Phorbol esters stimulate muscle glucose transport by a mechanism distinct from the insulin and hypoxia pathways. Hansen, P.A., Corbett, J.A., Holloszy, J.O. Am. J. Physiol. (1997) [Pubmed]
  6. EGF receptor affinity is regulated by intracellular calcium and protein kinase C. Fearn, J.C., King, A.C. Cell (1985) [Pubmed]
  7. Subunit interaction with PICK and GRIP controls Ca2+ permeability of AMPARs at cerebellar synapses. Liu, S.J., Cull-Candy, S.G. Nat. Neurosci. (2005) [Pubmed]
  8. Essential role for the PKC target MARCKS in maintaining dendritic spine morphology. Calabrese, B., Halpain, S. Neuron (2005) [Pubmed]
  9. 1,25-Dihydroxyvitamin D3 and 12-O-tetradecanoyl phorbol 13-acetate cause differential activation of Ca(2+)-dependent and Ca(2+)-independent isoforms of protein kinase C in rat colonocytes. Bissonnette, M., Wali, R.K., Hartmann, S.C., Niedziela, S.M., Roy, H.K., Tien, X.Y., Sitrin, M.D., Brasitus, T.A. J. Clin. Invest. (1995) [Pubmed]
  10. Casein kinase I alpha and alpha L: alternative splicing-generated kinases exhibit different catalytic properties. Zhang, J., Gross, S.D., Schroeder, M.D., Anderson, R.A. Biochemistry (1996) [Pubmed]
  11. Identification of cellular activation mechanisms associated with salivary secretion. Putney, J.W. Annu. Rev. Physiol. (1986) [Pubmed]
  12. ras-induced c-fos expression and proliferation in living rat fibroblasts involves C-kinase activation and the serum response element pathway. Gauthier-Rouvière, C., Fernandez, A., Lamb, N.J. EMBO J. (1990) [Pubmed]
  13. Characterization of pituitary calcium-activated, phospholipid-dependent protein kinase: redistribution by gonadotropin-releasing hormone. Naor, Z., Zer, J., Zakut, H., Hermon, J. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  14. Casein kinase 1 regulates connexin-43 gap junction assembly. Cooper, C.D., Lampe, P.D. J. Biol. Chem. (2002) [Pubmed]
  15. A noncanonical sequence phosphorylated by casein kinase 1 in beta-catenin may play a role in casein kinase 1 targeting of important signaling proteins. Marin, O., Bustos, V.H., Cesaro, L., Meggio, F., Pagano, M.A., Antonelli, M., Allende, C.C., Pinna, L.A., Allende, J.E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  16. Inhibition of voltage-gated K channels in synaptosomes by sn-1,2-dioctanoylglycerol, an activator of protein kinase C. Colby, K.A., Blaustein, M.P. J. Neurosci. (1988) [Pubmed]
  17. Cyclic adenosine monophosphate and diacylglycerol. Mutually inhibitory second messengers in cultured rat inner medullary collecting duct cells. Teitelbaum, I. J. Clin. Invest. (1990) [Pubmed]
  18. Hormone-mediated down-regulation of hepatic glutathione synthesis in the rat. Lu, S.C., Kuhlenkamp, J., Garcia-Ruiz, C., Kaplowitz, N. J. Clin. Invest. (1991) [Pubmed]
  19. Histamine secretion from rat enterochromaffinlike cells. Prinz, C., Kajimura, M., Scott, D.R., Mercier, F., Helander, H.F., Sachs, G. Gastroenterology (1993) [Pubmed]
  20. Differential targeting of protein kinase C and CaM kinase II signalings to vimentin. Ogawara, M., Inagaki, N., Tsujimura, K., Takai, Y., Sekimata, M., Ha, M.H., Imajoh-Ohmi, S., Hirai, S., Ohno, S., Sugiura, H. J. Cell Biol. (1995) [Pubmed]
  21. Nerve growth factor action is mediated by cyclic AMP- and Ca+2/phospholipid-dependent protein kinases. Cremins, J., Wagner, J.A., Halegoua, S. J. Cell Biol. (1986) [Pubmed]
  22. Involvement of protein kinase C epsilon in thyrotropin-releasing hormone-stimulated phosphorylation of the myristoylated alanine-rich C kinase substrate in rat pituitary clonal cells. Akita, Y., Kawasaki, H., Ohno, S., Suzuki, K., Kawashima, S. Electrophoresis (2000) [Pubmed]
  23. Effect of GnRH antagonists on phorbol ester-induced LH release from rat pituitary gonadotrophs. Saito, S., Izumi, S., Umeuchi, M., Makino, T., Tsujimoto, G., Nozawa, S. Endocr. J. (1994) [Pubmed]
  24. Glucose-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in isolated rat pancreatic islets. Calle, R., Ganesan, S., Smallwood, J.I., Rasmussen, H. J. Biol. Chem. (1992) [Pubmed]
  25. Coordination of membrane excitability through a GIRK1 signaling complex in the atria. Nikolov, E.N., Ivanova-Nikolova, T.T. J. Biol. Chem. (2004) [Pubmed]
  26. Facial motor neuron regeneration induces a unique spatial and temporal pattern of myristoylated alanine-rich C kinase substrate expression. McNamara, R.K., Jiang, Y., Streit, W.J., Lenox, R.H. Neuroscience (2000) [Pubmed]
  27. Phorbol ester stimulates calcitonin secretion synergistically with A23187, and additively with dibutyryl cyclic AMP in a rat C-cell line. Hishikawa, R., Fukase, M., Yamatani, T., Kadowaki, S., Fujita, T. Biochem. Biophys. Res. Commun. (1985) [Pubmed]
  28. Role of fos-AP-1 binding sequence (FAP) in the induction of c-fos expression by purified C-kinase and in c-fos down-regulation following serum induction. Gauthier-Rouvière, C., Basset, M., Lamb, N.J., Fernandez, A. Oncogene (1992) [Pubmed]
  29. Characterization of a C-kinase inhibitory fraction. Holian, O., Kumar, R., Nyhus, L.M. Biochem. Int. (1986) [Pubmed]
WikiGenes - Universities