RGD Reference Report - Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis. - Rat Genome Database

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Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis.

Authors: Conner, SD  Schmid, SL 
Citation: Conner SD and Schmid SL, J Cell Biol. 2002 Mar 4;156(5):921-9. Epub 2002 Mar 4.
RGD ID: 8553925
Pubmed: (View Article at PubMed) PMID:11877461
DOI: Full-text: DOI:10.1083/jcb.200108123

The mu 2 subunit of the AP2 complex is known to be phosphorylated in vitro by a copurifying kinase, and it has been demonstrated recently that mu 2 phosphorylation is required for transferrin endocytosis (Olusanya, O., P.D. Andrews, J.R. Swedlow, and E. Smythe. 2001. Curr. Biol. 11:896-900). However, the identity of the endogenous kinase responsible for this phosphorylation is unknown. Here we identify and characterize a novel member of the Prk/Ark family of serine/threonine kinases, adaptor-associated kinase (AAK)1. We find that AAK1 copurifies with adaptor protein (AP)2 and that it directly binds the ear domain of alpha-adaptin in vivo and in vitro. In neuronal cells, AAK1 is enriched at presynaptic terminals, whereas in nonneuronal cells it colocalizes with clathrin and AP2 in clathrin-coated pits and at the leading edge of migrating cells. AAK1 specifically phosphorylates the mu subunit in vitro, and stage-specific assays for endocytosis show that mu phosphorylation by AAK1 results in a decrease in AP2-stimulated transferrin internalization. Together, these results provide strong evidence that AAK1 is the endogenous mu 2 kinase and plays a regulatory role in clathrin-mediated endocytosis. These results also lend support to the idea that clathrin-mediated endocytosis is controlled by cycles of phosphorylation/desphosphorylation.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Aak1  (AP2 associated kinase 1)


Additional Information