Phosphatidylinositol(3)-Phosphate Signaling Mediated by Specific Binding to RING FYVE Domains
1998; Elsevier BV; Volume: 2; Issue: 1 Linguagem: Inglês
10.1016/s1097-2765(00)80125-2
ISSN1097-4164
AutoresChristopher G. Burd, Scott D. Emr,
Tópico(s)Protein Kinase Regulation and GTPase Signaling
ResumoPhosphoinositide 3-kinases (PI(3)K) are important regulators of receptor signaling cascades and intracellular membrane trafficking. To date, no protein domain has been identified that binds specifically to PtdIns(3)P and thereby recruits/activates downstream effectors of PtdIns(3)P signaling. Using an in vivo assay in yeast that detects Vps34 PI(3)K-dependent intracellular localization of a GFP reporter protein, and in vitro lipid-binding assays, we demonstrate that cysteine-rich RING domains of the FYVE finger subfamily bind specifically to PtdIns phosphorylated exclusively at the D-3 position of the inositol ring. GFP-FYVE domain fusion proteins localized predominantly to membranes of endocytic compartments and required active Vps34 PI(3)K. Our data establish a molecular link between Vps34 PI(3)K and several FYVE domain–containing proteins (Vac1p, Vps27p) required for vacuolar/lysosomal protein trafficking.
Referência(s)