Casein kinases

HSFl phosphorylation must be sensitive to nonheat inducers of HSF-DNA binding activity because HSFl phosphorylation can be achieved at 37 °C by other inducers of the HS response. HSF 1 contains polypeptide sequences that could serve as substrates for well characterized protein kinases, but few of these are known to be heat inducible. One family of protein kinases, the S6 protein kinases, have already been shown to exhibit heat inducible activity however, their peak level of activity during HS occurs well after the maximal induction of HSF phosphorylation (Jurivich et al., 1991). Thus, other protein kinases are likely to be directly linked to the phosphorylation of HSF. Some of the putative protein phosphorylation sites on HSF include motifs for protein kinase C, casein kinase, and enterokinase. There are tyrosine sequences that match substrates for known tyrosine kinases, but whether these residues are accessible to phosphorylation is not established. 

Miyata, Y. Yahara, I. (1992). The 90-kDa heat shock protein, hsp90, binds and protects casein kinase 11 from self aggregation and enhances its kinase activity. J. Biol. Chem. 267, 7042-7047. 

Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Glycogen Synthetase Kinase p56 Lymphoid T Cell Tyrosine Kinase Protein Kinase CK2 (Casein Kinase II)... 

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... 

The ability of DARPP-32 and inhibitor-1 to be phosphorylated at their PKA site is affected by phosphorylation at numerous other sites. DARPP-32 is phosphorylated by CDK5 and casein kinases I and II, all of which affect the phosphorylation state at Thr34. Inhibitor-1 also serves as a substrate of CDK5, at a site that is not homologous to the CDK5 site on DARPP-32. Further work is needed to understand the physiological significance of these other phosphorylation reactions. 

The effect of sphingosine on other enzymes may also contribute to its apoptotic effect. These include the inhibition of calcium/calmodulin-requiring enzymes and DNA primase and the stimulation of casein kinase II and several unidentified kinases (Alessenko, 2000). In addition, sphingosine can increase the cellular concentration of cyclic AMP, which is inhibitory for proliferation in many cell types (Pyne and Pyne, 1996). 

Difficulties in detecting nucleolin on the cell surface could be explained by its very low concentration in this compartment (Hovanessian et al, 2000). Moreover, this cell surface expressed nucleolin protein has a different isoelectric point and it is recognized by only one monoclonal antibody (mAb D3) in its native conformation (Hovanessian et al, 2000). This probably reflects specific post-translational modifications undergone by nucleolin on the cell surface. Consistent with this hypothesis, extracellular nucleolin is a substrate of ecto-protein kinases including casein kinase II (Dumler et al, 1999 Jordan et al., 1994). Interestingly, indirect evidence suggests... 

Dumler 1, Stepanova V, Jerke U, Mayboroda OA, Vogel F, Bouvet P, Tkachuk V, Haller H, Gulba DC (1999) Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin. Cutr Biol 9 1468-1476... 

Around the same time as bioinformatics revealed similarities between CSN, proteasome, and eIF3, Dubiel and coworkers, while trying to identify new components of the 26S proteasome, identified a novel protein complex that possessed protein kinase activity. They found that the new protein complex was capable of phosphor-ylating c-jun and IkKBq and the precursor of NFk-B was called pl05. Other protein kinases are found to interact with CSN as well. For example, inositol 1,3,4,-trisphosphate 5/6 kinase, casein kinase 2, and protein kinase D associate with CSN. " ... 

Wisniewski, J.R., Szewczuk, Z., Petry, I., Schwanbeck, R., and Renner, U. (1999) Constitutive phosphorylation of the acidic tails of the high mobility group 1 proteins by casein kinase II alters their conformation, stability, and DNA binding specificity. J Biol. Chem. 274, 20116-20122. 

CD28 response element casein kinase 2 circular dichroism... 

Lin JM, Kilman VL, Keegan K et al 2002 A role for casein kinase 2a in the Drosophila circadian clock. Nature 420 816-820... 

There is growing evidence that clock proteins are regulated dynamically in both temporal (production and degradation) and spatial (nuclear and cytoplasmic) dimensions. The phosphorylation of mPERl and mPER2 by casein kinase le (CKIe) is known as an important step for the accumulation of negatively active clock proteins (Lowrey et al 2000) as in Drosophila (Kloss et al 1998). 

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