Phosphorylation of Numb regulates its interaction with the clathrin-associated adaptor AP-2

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/4778
Title
Phosphorylation of Numb regulates its interaction with the clathrin-associated adaptor AP-2
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Description

Numb is thought to participate in clathrin-dependent endocytosis by directly interacting with the clathrin-associated adaptor complex AP-2, although the underlying mechanisms are unknown. Numb is also known to be phosphorylated at Ser264 in vitro and in vivo. Here, we found that Numb is phosphorylated in vitro by Ca2+/calmodulin-dependent protein kinase I on Ser283. This phosphorylation was also observed in transfected COS-7 cells, indicating its physiological relevance. Pull-down experiments showed that the phosphorylation of Numb impaired its binding to the AP-2 complex and simultaneously recruited 14-3-3 proteins in vitro. Based on experiments using Numb mutants, both the initial phosphorylation of Ser264 and the subsequent phosphorylation of Ser283 are sufficient to abolish the binding of Numb to AP-2 and to promote the interaction with 14-3-3 protein. These findings suggest a novel mechanism for the regulation of Numb-mediated endocytosis, namely through direct phosphorylation.

Author
著者 Tokumitsu Hiroshi
著者(ヨミ) トクミツ ヒロシ
著者(別表記) 徳光 浩
著者 Hatano Naoya
著者(ヨミ) ハタノ ナオヤ
著者(別表記) 波多野 直哉
著者 Yokokura Shigeyuki
著者(ヨミ) ヨコクラ シゲユキ
著者(別表記) 横倉 繁行
著者 Sueyoshi Yuka
著者(ヨミ) スエヨシ ユカ
著者(別表記) 末吉 由佳
著者 Nozaki Naohito
著者(ヨミ) ノザキ ナオヒト
著者(別表記) 野崎 直仁
著者 Kobayashi Ryoji
著者(ヨミ) コバヤシ リョウジ
著者(別表記) 小林 良二
Publication Title
FEBS letters
Volume
580
Issue
24
Start Page
5791
End Page
5801
Publisher
Elsevier
Published Date
20061016
ISSN
0014-5793
NCID
AA00642943
DOI
10.1016/j.febslet.2006.09.043
Resource Type
Journal Article
Language
eng
Resource URL
http://dx.doi.org/10.1016/j.febslet.2006.09.043
Rights
Copyright c 2006 Elsevier Ltd
Text Version
author
Set
香川大学
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