Portal de Periódicos da CAPES

Odin (ANKS1A) Modulates EGF Receptor Recycling and Stability

2013; Public Library of Science; Volume: 8; Issue: 6 Linguagem: Inglês

10.1371/journal.pone.0064817

1932-6203

Jiefei Tong, Yaroslav Sydorskyy, Jonathan St‐Germain, Paul Taylor, Ming‐Sound Tsao, Michael F. Moran,

Cell Adhesion Molecules Research

The ANKS1A gene product, also known as Odin, was first identified as a tyrosine-phosphorylated component of the epidermal growth factor receptor network. Here we show that Odin functions as an effector of EGFR recycling. In EGF-stimulated HEK293 cells tyrosine phosphorylation of Odin was induced prior to EGFR internalization and independent of EGFR-to-ERK signaling. Over-expression of Odin increased EGF-induced EGFR trafficking to recycling endosomes and recycling back to the cell surface, and decreased trafficking to lysosomes and degradation. Conversely, Odin knockdown in both HEK293 and the non-small cell lung carcinoma line RVH6849, which expresses roughly 10-fold more EGF receptors than HEK293, caused decreased EGFR recycling and accelerated trafficking to the lysosome and degradation. By governing the endocytic fate of internalized receptors, Odin may provide a layer of regulation that enables cells to contend with receptor cell densities and ligand concentration gradients that are physiologically and pathologically highly variable.