12890670

Source:http://linkedlifedata.com/resource/pubmed/id/12890670

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0113519, umls-concept:C0256371, umls-concept:C0851285, umls-concept:C1719914, umls-concept:C2828406
pubmed:issue	41
pubmed:dateCreated	2003-10-6
pubmed:abstractText	Diacylglycerol kinase (DGK) terminates diacylglycerol (DAG) signaling by phosphorylating DAG to produce phosphatidic acid, which also has signaling properties. Thus, precise control of DGK activity is essential for proper signal transduction. We demonstrated previously that a peptide corresponding to the myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation site domain (PSD) in DGK zeta was phosphorylated in vitro by an active fragment of protein kinase C (PKC). In the present study, we tested full-length DGK zeta and found that PKC alpha phosphorylated DGK zeta on serines within the MARCKS PSD in vitro and in vivo. DGK zeta also coimmunoprecipitated with PKC alpha, suggesting that they reside in a regulated signaling complex. We then tested whether phosphorylation affected DAG kinase activity. We found that a mutant (DGK zeta S/D) in which serines within the MARCKS PSD were altered to aspartates (to mimic phosphorylation) had lower activity compared with wild-type DGK zeta or a control mutant (DGK zeta S/N) in which the same serines were changed to asparagines. Furthermore, activation of PKC alpha by phorbol 12-myristate 13-acetate inhibited the activity of wild-type DGK zeta, but not DGK zeta S/D, in human embryonic kidney 293 cells. These results suggest that by phosphorylating the MARCKS PSD, PKC alpha attenuates DGK zeta activity. Supporting this, we found that cells expressing DGK zeta S/D had higher DAG levels and grew more rapidly compared with cells expressing DGK zeta S/N that could not be phosphorylated. Taken together, these results indicate that PKC alpha phosphorylates DGK zeta in cells, and this phosphorylation inhibits its kinase activity to remove cellular DAG, thereby affecting cell growth.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/2985121R
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Diacylglycerol Kinase, http://linkedlifedata.com/resource/pubmed/chemical/Diglycerides, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PRKCA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases, http://linkedlifedata.com/resource/pubmed/chemical/myristoylated alanine-rich C...
pubmed:status	MEDLINE
pubmed:month	Oct
pubmed:issn	0021-9258
pubmed:author	pubmed-author:NiuJ LJL, pubmed-author:PrescottStephen MSM, pubmed-author:TophamMatthew KMK
pubmed:issnType	Print
pubmed:day	10
pubmed:volume	278
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	39542-7
pubmed:dateRevised	2009-11-19
pubmed:meshHeading	pubmed-meshheading:12890670-Binding Sites, pubmed-meshheading:12890670-Cell Division, pubmed-meshheading:12890670-Cell Line, pubmed-meshheading:12890670-Diacylglycerol Kinase, pubmed-meshheading:12890670-Diglycerides, pubmed-meshheading:12890670-Humans, pubmed-meshheading:12890670-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:12890670-Membrane Proteins, pubmed-meshheading:12890670-Phospholipase C gamma, pubmed-meshheading:12890670-Phosphorylation, pubmed-meshheading:12890670-Protein Kinase C, pubmed-meshheading:12890670-Protein Kinase C-alpha, pubmed-meshheading:12890670-Protein Structure, Tertiary, pubmed-meshheading:12890670-Proteins, pubmed-meshheading:12890670-Recombinant Proteins, pubmed-meshheading:12890670-Signal Transduction, pubmed-meshheading:12890670-Tetradecanoylphorbol Acetate, pubmed-meshheading:12890670-Type C Phospholipases
pubmed:year	2003
pubmed:articleTitle	Protein kinase C alpha phosphorylates and negatively regulates diacylglycerol kinase zeta.
pubmed:affiliation	Huntsman Cancer Institute, and Department of Oncological Sciences, University of Utah, Salt Lake City, Utah 84112, USA.
pubmed:publicationType	Journal Article, In Vitro, Research Support, Non-U.S. Gov't