Numb3 is an endocytosis adaptor for the inflammatory marker P-selectin

Biochemical and Biophysical Research Communications
Thomas SchlüterRalf Bohnensack

Abstract

The endocytic protein Numb3 was found to bind to the cytosolic tail of the leukocyte adhesion receptor P-selectin. The N-terminal phosphotyrosine-binding (PTB) domain of Numb3 is responsible for this activity. An alanine scan revealed the FTNAAFD sequence as recognition region in P-selectin. Structural modeling of the interaction between the Numb PTB domain and the P-selectin tail suggests that both phenylalanines within the recognition sequence fit into hydrophobic cavities of the PTB surface. Their exchange for alanine gave Numb-negative mutants detaining the inhibition of P-selectin endocytosis by Numb PTB overexpression. Cells stable expressing P-selectins internalized the negative mutants markedly slower than the wild type. Consistent with other reports on the phosphorylation of Numb, we found that only the dephospho-Numb is able to bind P-selectin. Our observations demonstrate that Numb3 is an endocytic receptor for P-selectin and may be responsible for the rapid internalization of P-selectin when endothelial activation ends.

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Citations

Aug 22, 2009·Nature Reviews. Molecular Cell Biology·Linton M Traub
Jul 1, 2016·Journal of Cell Science·Jin-Feng SuJie Luo
Nov 9, 2018·Oncotarget·Amber GondaNathan R Wall
Jul 7, 2017·BioMed Research International·János Kappelmayer, Béla Nagy

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