RGD Reference Report - Phosphorylation of Numb regulates its interaction with the clathrin-associated adaptor AP-2. - Rat Genome Database

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

Authors: Tokumitsu, H  Hatano, N  Yokokura, S  Sueyoshi, Y  Nozaki, N  Kobayashi, R 
Citation: Tokumitsu H, etal., FEBS Lett. 2006 Oct 16;580(24):5797-801. Epub 2006 Sep 27.
RGD ID: 2302412
Pubmed: PMID:17022975   (View Abstract at PubMed)
DOI: DOI:10.1016/j.febslet.2006.09.043   (Journal Full-text)

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 Ser(264)in vitro and in vivo. Here, we found that Numb is phosphorylated in vitro by Ca(2+)/calmodulin-dependent protein kinase I on Ser(283). 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 Ser(264) and the subsequent phosphorylation of Ser(283) 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.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q3MUI12302412; 2302412PMID:17022975IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Ap2b1  (adaptor related protein complex 2 subunit beta 1)
Ywhah  (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta)

Objects referenced in this article
Gene Ap2a2 adaptor related protein complex 2 subunit alpha 2 Rattus norvegicus
Gene Nudc nuclear distribution C, dynein complex regulator Rattus norvegicus

Additional Information