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Simulation of the regulation of EGFR endocytosis and EGFR‐ERK signaling by endophilin‐mediated RhoA‐EGFR crosstalk
Author(s) -
Ung Choong Yong,
Li Hu,
Ma Xiao Hua,
Jia Jia,
Li Bao Wen,
Low Boon Chuan,
Chen Yu Zong
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.05.026
Subject(s) - rhoa , endocytosis , microbiology and biotechnology , crosstalk , small gtpase , mapk/erk pathway , gtpase , chemistry , signal transduction , biology , cancer research , cell , biochemistry , physics , optics
Deregulations of EGFR endocytosis in EGFR‐ERK signaling are known to cause cancers and developmental disorders. Mutations that impaired c‐Cbl–EGFR association delay EGFR endocytosis and produce higher mitogenic signals in lung cancer. ROCK, an effector of small GTPase RhoA was shown to negatively regulate EGFR endocytosis via endophilin A1. A mathematical model was developed to study how RhoA and ROCK regulate EGFR endocytosis. Our study suggested that over‐expressing RhoA as well as ROCK prolonged ERK activation partly by reducing EGFR endocytosis. Overall, our study hypothesized an alternative role of RhoA in tumorigenesis in addition to its regulation of cytoskeleton and cell motility.