Abstract：
:Synthesis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPgammaS-dependent activator of PI(4)P5Kalpha is the small G protein ADP-ribosylation factor (ARF) and that the activation strictly requires phosphatidic acid, the product of phospholipase D (PLD). In vivo, ARF6, but not ARF1 or ARF5, spatially coincides with PI(4)P5Kalpha. This colocalization occurs in ruffling membranes formed upon AIF4 and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cdelta1, indicating locally elevated PI(4,5)P2. Thus, PI(4)P5Kalpha is a downstream effector of ARF6 and when ARF6 is activated by agonist stimulation, it triggers recruitment of a diverse but interactive set of signaling molecules into sites of active cytoskeletal and membrane rearrangement.
journal_name
Celljournal_title
Cellauthors
Honda A,Nogami M,Yokozeki T,Yamazaki M,Nakamura H,Watanabe H,Kawamoto K,Nakayama K,Morris AJ,Frohman MA,Kanaho Ydoi
10.1016/s0092-8674(00)81540-8subject
Has Abstractpub_date
1999-11-24 00:00:00pages
521-32issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(00)81540-8journal_volume
99pub_type
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