title: Odin (ANKS1A) modulates EGF receptor recycling and stability.
abstract: 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.
authors.affiliation: Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Canada.
authors.forename: Jiefei
authors.initials: J
authors.lastname: Tong
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Sydorskyy
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: St-Germain
authors.forename: Paul
authors.initials: P
authors.lastname: Taylor
authors.forename: Ming S
authors.initials: MS
authors.lastname: Tsao
authors.forename: Michael F
authors.initials: MF
authors.lastname: Moran
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D011992:Endosomes / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D010766:Phosphorylation; D021381:Protein Transport / Q000235:genetics / Q000502:physiology
chemical_list: C557872:ANKS1A protein, human; D048868:Adaptor Proteins, Signal Transducing; C512478:EGFR protein, human; D066246:ErbB Receptors