Consequences of replacing EGFR juxtamembrane domain with an unstructured sequence

Research output: Contribution to journalArticle

Abstract

EGFR is the best studied receptor tyrosine kinase. Yet, a comprehensive mechanistic understanding of EGFR signaling is lacking, despite very active research in the field. In this paper, we investigate the role of the juxtamembrane (JM) domain in EGFR signaling by replacing it with a (GGS) 10 unstructured sequence. We probe the effect of this replacement on (i) EGFR phosphorylation, (ii) EGFR dimerization and (iii) ligand (EGF) binding. We show that the replacement of EGFR JM domain with a (GGS) 10 unstructured linker completely abolishes the phosphorylation of all tyrosine residues, without measurable effects on receptor dimerization or ligand binding. Our results suggest that the JM domain does not stabilize the inactive EGFR dimer in the absence of ligand, and is likely critical only for the last step of EGFR activation, the ligand-induced transition from the inactive to active dimer.

Original languageEnglish (US)
Article number854
JournalScientific Reports
Volume2
DOIs
StatePublished - 2012

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Ligands
Dimerization
Phosphorylation
Receptor Protein-Tyrosine Kinases
Epidermal Growth Factor
Tyrosine
Research

ASJC Scopus subject areas

  • General

Cite this

Consequences of replacing EGFR juxtamembrane domain with an unstructured sequence. / He, Lijuan; Hristova, Kalina A.

In: Scientific Reports, Vol. 2, 854, 2012.

Research output: Contribution to journalArticle

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