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Intersectin‐s interaction with DENND2B facilitates recycling of epidermal growth factor receptor
Author(s) -
Ioannou Maria S,
Kulasekaran Gopinath,
Fotouhi Maryam,
Morein Justin J,
Han Chanshuai,
Tse Sarah,
Nossova Nadya,
Han Tony,
Mannard Erin,
McPherson Peter S
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744034
Subject(s) - epidermal growth factor receptor , microbiology and biotechnology , biology , business , receptor , genetics
Epidermal growth factor ( EGF ) activates the EGF receptor ( EGFR ) and stimulates its internalization and trafficking to lysosomes for degradation. However, a percentage of EGFR undergoes ligand‐independent endocytosis and is rapidly recycled back to the plasma membrane. Importantly, alterations in EGFR recycling are a common hallmark of cancer, and yet, our understanding of the machineries controlling the fate of endocytosed EGFR is incomplete. Intersectin‐s is a multi‐domain adaptor protein that is required for internalization of EGFR . Here, we discover that intersectin‐s binds DENND 2B, a guanine nucleotide exchange factor for the exocytic GTP ase Rab13, and this interaction promotes recycling of ligand‐free EGFR to the cell surface. Intriguingly, upon EGF treatment, DENND 2B is phosphorylated by protein kinase D and dissociates from intersectin‐s, allowing for receptor targeting to degradation. Our study thus reveals a novel mechanism controlling the fate of internalized EGFR with important implications for cancer.