Reactome | Dissociation of AAK1 and dephosphorylation of AP-2 mu2

Dissociation of AAK1 and dephosphorylation of AP-2 mu2

Stable Identifier

R-HSA-8871193

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

clathrin-coated endocytic vesicle membrane

ReviewStatus

5/5

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Dissociation of AAK1 and dephosphorylation of AP-2 mu2

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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
16103228	An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway Wilm, M, Christoforidis, S, Wenk, MR, Hoepfner, S, Hayashi, M, Zerial, M, Nystuen, A, Shin, HW, Lacas-Gervais, S, Solimena, M, Frankel, WN, Uttenweiler-Joseph, S, De Camilli, P, Modregger, J	J. Cell Biol.	2005
15895077	Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit Sato, K, Grant, BD, Fonarev, P, Sato, M, Huang, CJ, Liou, W	Nat. Cell Biol.	2005
10559924	Phosphatidylinositol-3-OH kinases are Rab5 effectors Zhao, L, Waterfield, MD, Miaczynska, M, Yip, SC, Zerial, M, Backer, JM, Wilm, M, Ashman, K, Christoforidis, S	Nat Cell Biol	1999
18981233	Coordinated regulation of AP2 uncoating from clathrin-coated vesicles by rab5 and hRME-6 Grant, BD, Schiavo, G, Fonarev, P, Smythe, E, Shortt, B, Singh, S, Maxwell, E, Hansen, J, Semerdjieva, S	J. Cell Biol.	2008