Recruitment of epidermal growth factor receptors into coated pits requires their activated tyrosine kinase

Christophe Lamaze, Sandra L. Schmid

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

EGF-receptor (EGF-R) tyrosine kinase is required for the down-regulation of activated EGF-R. However, controversy exists as to whether ligand-induced activation of the EGF-R tyrosine kinase is required for internalization or for lysosomal targeting. We have addressed this issue using a cell-free assay that selectively measures the recruitment of EGF-R into coated pits. Here we show that EGF bound to wild-type receptors is efficiently sequestered in coated pits. In contrast, sequestration of kinase-deficient receptors occurs inefficiently and at the same basal rate of endocytosis of unoccupied receptors or receptors lacking any cytoplasmic domain. Sequestration of deletion mutants of the EGF-R that lack autophosphorylation sites also requires an active tyrosine kinase. This suggests that a tyrosine kinase substrate(s) other than the EGF-R itself, is required for its efficient ligand-induced recruitment into coated pits. Addition of a soluble EGF-R tyrosine kinase fully and specifically restores the recruitment of kinase- deficient EGF-R into coated pits providing a powerful functional assay for identification of these substrate(s).

Original languageEnglish (US)
Pages (from-to)47-54
Number of pages8
JournalJournal of Cell Biology
Volume129
Issue number1
DOIs
StatePublished - Apr 1995

ASJC Scopus subject areas

  • Cell Biology

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