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CSNK1A1  -  casein kinase 1, alpha 1

Gallus gallus

 
 
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Disease relevance of CSNK1A1

  • L. major CK1 isoform 2 expressed as a recombinant protein in Escherichia coli displayed biochemical and inhibition characteristics similar to those of the purified native enzyme [1].
 

High impact information on CSNK1A1

  • Biochemical studies have led to the unexpected discovery that an isoform of CK1 represents the primary target of the pyrrole and imidazopyridine kinase inhibitors in these organisms [1].
  • Casein kinase 1 (CK1) is a family of multifunctional Ser/Thr protein kinases that are ubiquitous in eukaryotic cells [1].
  • In addition, norepinephrine causes the rapid translocation of C kinase activity from cytosolic to membrane associated distribution, consistent with its rapid activation in response to applied neurotransmitter [2].
  • This compound also activates C kinase and binds competitively to the phorbol ester receptor, yet does not affect cell differentiation [3].
  • The ability of phorbol esters to promote tumor formation and alter cell differentiation has been attributed to its action on a number of critical cellular functions, in particular, on protein phosphorylation, through the activation of protein C kinase [3].
 

Anatomical context of CSNK1A1

  • Basing on these data it can be presumed that PKA activity increases, but the levels of CK2 and CK1 decrease during chick embryo development [4].
 

Analytical, diagnostic and therapeutic context of CSNK1A1

  • The results described here warrant further evaluation of the activity of these kinase inhibitors against mammalian stage Leishmania parasites in vitro and in animal models of infection, as well as studies to genetically validate CK1 as a therapeutic target in trypanosomatid parasites [1].
  • Further purification of CK1 activity from L. major and characterization via liquid chromatography coupled tandem mass spectrometry identified CK1 isoform 2 as the specific parasite protein inhibited by imidazopyridines [1].

References

  1. Inhibitors of casein kinase 1 block the growth of Leishmania major promastigotes in vitro. Allocco, J.J., Donald, R., Zhong, T., Lee, A., Tang, Y.S., Hendrickson, R.C., Liberator, P., Nare, B. Int. J. Parasitol. (2006) [Pubmed]
  2. Activation of phosphoinositide turnover and protein kinase C by neurotransmitters that modulate calcium channels in embryonic chick sensory neurons. Harish, O.E., Role, L.W. Int. J. Dev. Neurosci. (1992) [Pubmed]
  3. Effect of phorbol and bryostatin I on chondrogenic expression of chick limb bud, in vitro. Garrison, J.C., Pettit, G.R., Uyeki, E.M. Life Sci. (1987) [Pubmed]
  4. SDS/PAGE characteristics of protein kinases tightly associated with chick embryo brain ribosomes. Sanecka-Obacz, M. Acta Biochim. Pol. (1999) [Pubmed]
 
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