The lipid second messenger diacylglycerol as a negative regulator of Rac signalling.
We have established a novel role for the second messenger DAG (diacylglycerol), a product of PtdIns(4,5)P2 hydrolysis by PLC (phospholipase C). In addition to its well-known function as a protein kinase C activator, DAG produced by stimulation of the epidermal growth factor receptor causes the redistribution of the Rac-GAP (GTPase-activating protein) beta2-chimaerin to the plasma membrane, where it associates with the active form of Rac1 and promotes the inactivation of this small G-protein. This represents the first example of a Rac-GAP regulated directly by DAG in response to the activation of a tyrosine kinase receptor, and suggests a previously unappreciated role for this lipid as a negative modulator of Rac signalling.
Wang
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Department of Pharmacology, University of Pennsylvania School of Medicine, 816 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104-6160, USA.
Kazanietz
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MG
D000818:Animals; D004075:Diglycerides / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology; D006706:Homeostasis; D009363:Neoplasm Proteins / Q000502:physiology; D051966:Phospholipase C gamma / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology; D015290:Second Messenger Systems; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000502:physiology*
D004075:Diglycerides; D009363:Neoplasm Proteins; D011955:Receptors, Drug; C079844:beta-chimaerin; C027776:phorbol ester receptor; D066246:ErbB Receptors; D011493:Protein Kinase C; D010740:Phospholipases; D051966:Phospholipase C gamma; D020744:rac GTP-Binding Proteins