Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation.
Cell
; 99(5): 521-32, 1999 Nov 24.
Article
en En
| MEDLINE
| ID: mdl-10589680
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Membrana Celular
/
Fosfotransferasas (Aceptor de Grupo Alcohol)
/
Fosfatidilinositol 4,5-Difosfato
/
Factores de Ribosilacion-ADP
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
1999
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos