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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0031727,
umls-concept:C0032433,
umls-concept:C0035820,
umls-concept:C0108555,
umls-concept:C0205263,
umls-concept:C0220905,
umls-concept:C0392747,
umls-concept:C0443172,
umls-concept:C1167622,
umls-concept:C1441414,
umls-concept:C1514562,
umls-concept:C1553874,
umls-concept:C1578820,
umls-concept:C1711351,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C1948023
|
| pubmed:issue |
33
|
| pubmed:dateCreated |
1997-9-4
|
| pubmed:abstractText |
The means by which the cell regulates protein kinase CK2 remain obscure. However, natural polyamines, cellular compounds required for cell proliferation, have been reported to strongly stimulate CK2-mediated phosphorylation of a number of substrates. Using spermine analogs, we have shown that polyamines directly interact with the CK2 beta subunit, and the chemical features of the highly acidic binding site (Asp51-Tyr80) have been determined. In the present study, we show that the isolated beta subunit region extending from residue Asp51 to Pro110 exhibits a specific and efficient polyamine binding activity similar to that of the entire beta subunit. Moreover, the replacement of Glu60, Glu61, and Glu63 of the beta subunit by 3 alanine residues leads to a loss of the spermine-induced stimulation of CK2 activity which correlates with a decrease in spermine binding affinity. Thermal stability studies indicate that the binding of spermine induces a 4 degrees C decrease of the Tm value for the holoenzyme. This was confirmed by circular dichroism analyses, which show that the 6 degrees C negative shift of the CK2 Tm value provoked by spermine binding, reflects a conformational change in the kinase. Together, these observations strongly suggest that this newly defined polyamine-binding domain is involved in the intrasteric regulation of CK2 activity.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
272
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
20820-7
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9252407-Animals,
pubmed-meshheading:9252407-Binding Sites,
pubmed-meshheading:9252407-COS Cells,
pubmed-meshheading:9252407-Casein Kinase II,
pubmed-meshheading:9252407-Coenzymes,
pubmed-meshheading:9252407-Enzyme Stability,
pubmed-meshheading:9252407-Mutagenesis, Site-Directed,
pubmed-meshheading:9252407-Protein Conformation,
pubmed-meshheading:9252407-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9252407-Spermine,
pubmed-meshheading:9252407-Structure-Activity Relationship
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Binding of polyamines to an autonomous domain of the regulatory subunit of protein kinase CK2 induces a conformational change in the holoenzyme. A proposed role for the kinase stimulation.
|
| pubmed:affiliation |
Laboratoire de Biochimie des Régulations Cellulaires Endocrines, Département de Biologie Moléculaire et Structurale, INSERM Unité 244, CEA Grenoble, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|