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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-1-4
pubmed:abstractText
Ceramide kinase (CERK) is essential for production of ceramide-1-phosphate (C1P), a bioactive lipid whose formation critically modulates ceramide levels. To explore how CERK is regulated, we used insect cell-expressed, recombinant hCERK and searched for post-translational modifications, using mass-spectrometry techniques. This led to identification of two phosphorylated serine residues, at positions 340 and 408. Point mutations preventing phosphorylation at either of these sites did not lead to detectable changes in subcellular localization or activity. However, preventing phosphorylation at S340 resulted in CERK instability as revealed by the behavior of the S340A mutant protein under various assay conditions in vitro. Phosphorylation of a cognate serine residue in sphingosine kinases was previously shown to be important. Therefore, phosphorylation within a conserved "regulation loop" downstream of the catalytic domain emerges as a new paradigm for regulation of kinases of the diacylglycerol kinase family. This "regulation loop" is reminiscent of the "activation loop" that controls AGC protein kinases, being a similar distance from the critical ATP binding site determinants in the primary sequence.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1535-3907
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
420-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Ceramide kinase profiling by mass spectrometry reveals a conserved phosphorylation pattern downstream of the catalytic site.
pubmed:affiliation
Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18, A-1090 Vienna, Austria.
pubmed:publicationType
Journal Article