Dissociation of AAK1 and dephosphorylation of AP-2 mu2

Stable Identifier
R-HSA-8871193
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

GAPVD1 binds the alpha adaptin ear domain of AP-2 mu2, activating its RAB5-directed GEF activity and displacing AAK1. AAK1 displacement results in a net dephosphorylation of the AP-2 mu2 subunit, destabilizing the interaction of AP-2 with the vesicle membrane (Sato et al, 2005; Smerdjieva et al, 2008). In addition, RAB5 contributes to PI(4,5)P2 turnover through recruitment of a PI3K or PI phosphatase, and this also destabilizes the interaction of AP-2 with the membrane (Smerdjieva et al, 2008; Christoforidis et al, 1999; Shin et al, 2005).

Literature References
PubMed ID Title Journal Year
15895077 Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit

Sato, M, Sato, K, Fonarev, P, Huang, CJ, Liou, W, Grant, BD

Nat. Cell Biol. 2005
16103228 An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway

Shin, HW, Hayashi, M, Christoforidis, S, Lacas-Gervais, S, Hoepfner, S, Wenk, MR, Modregger, J, Uttenweiler-Joseph, S, Wilm, M, Nystuen, A, Frankel, WN, Solimena, M, De Camilli, P, Zerial, M

J. Cell Biol. 2005
10559924 Phosphatidylinositol-3-OH kinases are Rab5 effectors

Christoforidis, S, Miaczynska, M, Ashman, K, Wilm, M, Zhao, L, Yip, SC, Waterfield, MD, Backer, JM, Zerial, M

Nat Cell Biol 1999
18981233 Coordinated regulation of AP2 uncoating from clathrin-coated vesicles by rab5 and hRME-6

Semerdjieva, S, Shortt, B, Maxwell, E, Singh, S, Fonarev, P, Hansen, J, Schiavo, G, Grant, BD, Smythe, E

J. Cell Biol. 2008
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