Cell 1999,
PMID: 10589680
Honda, A; Nogami, M; Yokozeki, T; Yamazaki, M; Nakamura, H; Watanabe, H; Kawamoto, K; Nakayama, K; Morris, A J; Frohman, M A; Kanaho, Y
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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Text Mining Data
Dashed line = No text mining data
Manually curated Databases
-
IRef Hprd Interaction:
ARF5
—
PIP5K1A
(in vitro)
-
IRef Hprd Interaction:
ARF6
—
PIP5K1A
(in vitro)
-
IRef Hprd Interaction:
ARF6
—
PIP5K1A
(in vivo)
-
IRef Hprd Interaction:
PIP5K1A
—
ARF1
(in vitro)
-
NCI Pathway Database Arf6 downstream pathway:
ARF6/GTP complex (ARF6)
→
PIP5K1A (PIP5K1A)
(modification, activates)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Arf6 downstream pathway:
ARF6/GTP complex (ARF6)
→
None
(modification, activates)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Arf6 downstream pathway:
ARF6/GTP complex (ARF6)
→
PLD1-2 (PLD2/PLD1)
(modification, activates)
Evidence: mutant phenotype, assay
In total, 5 gene pairs are associated to this article in curated databases