NDLI: Diacylglycerol Kinase ζ Regulates Ras Activation by a Novel Mechanism

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Diacylglycerol Kinase ζ Regulates Ras Activation by a Novel Mechanism

Content Provider	Scilit
Author	Topham, Matthew K. Prescott, Stephen M.
Copyright Year	2001
Description	Guanine nucleotide exchange factors (GEFs) activate Ras by facilitating its GTP binding. Ras guanyl nucleotide-releasing protein (GRP) was recently identified as a Ras GEF that has a diacylglycerol (DAG)-binding C1 domain. Its exchange factor activity is regulated by local availability of signaling DAG. DAG kinases (DGKs) metabolize DAG by converting it to phosphatidic acid. Because they can attenuate local accumulation of signaling DAG, DGKs may regulate RasGRP activity and, consequently, activation of Ras. DGKζ, but not other DGKs, completely eliminated Ras activation induced by RasGRP, and DGK activity was required for this mechanism. DGKζ also coimmunoprecipitated and colocalized with RasGRP, indicating that these proteins associate in a signaling complex. Coimmunoprecipitation of DGKζ and RasGRP was enhanced in the presence of phorbol esters, which are DAG analogues that cannot be metabolized by DGKs, suggesting that DAG signaling can induce their interaction. Finally, overexpression of kinase-dead DGKζ in Jurkat cells prolonged Ras activation after ligation of the T cell receptor. Thus, we have identified a novel way to regulate Ras activation: through DGKζ, which controls local accumulation of DAG that would otherwise activate RasGRP.
Related Links	http://jcb.rupress.org/content/152/6/1135.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199204/pdf http://jcb.rupress.org/content/jcb/152/6/1135.full.pdf
Ending Page	1144
Page Count	10
Starting Page	1135
DOI	10.1083/jcb.152.6.1135
Journal	Journal of Cell Biology
Issue Number	6
Volume Number	152
Language	English
Publisher	Rockefeller University Press
Publisher Date	2001-03-12
Access Restriction	Open
Subject Keyword	Immunology Cumulant Diacylglycerol Kinase Nucleotides Jurkat Cells Cell Line Actins Signal Transduction Transfection Guanine Nucleotide Exchange Factors Guanine Nucleotide Exchange Factor Dna Binding Proteins Protein Kinase C T Cell Receptor Journal: Journal of Cell Biology (Vol- 152, Issue- 6)
Content Type	Text

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