AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis.

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Citation

Sorensen EB, Conner SD

AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis.

Traffic. 2008 Sep;9(10):1791-800. doi: 10.1111/j.1600-0854.2008.00790.x. Epub 2008 Jul 24.

PubMed ID
18657069 [ View in PubMed
]
Abstract

Numb is an endocytic protein that is proposed to influence clathrin-coated pit assembly, although its mode of action and the mechanisms that regulate its activity are unknown. In this study, we show that Numb binds to and is phosphorylated by adaptor-associated kinase 1 (AAK1), a key endocytic kinase. We find that AAK1 redistributes Numb to perinuclear endosomes when overexpressed, while kinase depletion causes Numb to accumulate at the plasma membrane. Overexpression of a Numb point mutant (T102A) that lacks the AAK1 phosphorylation site potently disrupts transferrin and low-density lipoprotein internalization but does not impact EGF uptake. Consistent with Numb redistribution results, we find that T102A Numb no longer localizes to perinuclear endosomes. Instead, it is enriched at the plasma membrane where it shows elevated levels of colocalization with coated pit markers. Collectively, these observations demonstrate that Numb endocytic activity is regulated by AAK1 and that phosphorylation may be a critical step in promoting coated pit maturation.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
AP2-associated protein kinase 1Q2M2I8Details