Simulation of the regulation of EGFR endocytosis and EGFR-ERK signaling by endophilin-mediated RhoA-EGFR crosstalk

Choong Yong Ung, Hu Li, Xiao Hua Ma, Jia Jia, Bao Wen Li, Boon Chuan Low, Yu Zong Chen

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2283-2290
Number of pages8
JournalFEBS Letters
Volume582
Issue number15
DOIs
StatePublished - Jun 25 2008

Keywords

  • EGFR endocytosis
  • ERK activation
  • Pathway simulation
  • ROCK
  • RhoA

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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