Casein kinase phosphorylation role

Activation of cells results in the release of IKB, followed by the rapid proteolysis of IKB. Although phosphorylation of serine 32 and 36 in the amino-terminal part of IKBa occurs when the proinflammatory cytokines or mitogens are administered to a T lymphocytic cell line, a different site of action has been found after H2O2 incubation (Schoonbroodt et al., 2000). The tyrosine residue 42 and the C-terminal PEST (Pro-Glu-Ser-Thr) domain plays a major role in the phosphorlylation of IKB after treatment with H2O2. Furthermore the CVinducible phosphorylation was not dependent upon IKB kinase activation but involved casein kinase II. The importance of iron for the activation of NFKB was underlined by the fact that... 

FIG. 5. Role of phosphorylation and degradation of clock protein PER in human normal fibroblasts. After the phosphorylation of hPERl by casein kinase, the ubiquitin-proteosome pathway may be involved in its degradation in human cells. 

A genetic screen for novel clock mutations in Drosophila sA to the discovery of the first kinase that plays a role in circadian rhythmicity (Price et al 1998). Doubletime dht) is a member of the casein kinase 1 (CKl) family, and is 86% identical to human casein kinase Is (CKls) within the kinase domain (Kloss et al 1998). Originally, two mutations were isolated that produce short (18 h dht ) and long (27 h dbt ) behavioural rhythms. Since then, many period-altering mutations and loss-of-function alleles have been described. The majority of these mutations reside in the kinase domain of dbt, altering its ability to bind and/or phosphorylate its substrate (Fig. 1). All of the DBT point mutations analysed alter the phosphorylation state and accumulation of PER, indicating that DBT affects... 

Jaffe, L., Ryoo, H.D., Mann, R.S. 1997. A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila. Genes Dev. 11, 1327-1340. 

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