The transmembrane molecule kekkon 1 acts in a feedback loop to negatively regulate the activity of the Drosophila EGF receptor during oogenesis

Christian Ghiglione, Kermit L Carraway, Laufey T. Amundadottir, Robert E. Boswell, Norbert Perrimon, Joseph B. Duffy

Research output: Contribution to journalArticle

168 Scopus citations

Abstract

We have identified the Drosophila transmembrane molecule kekkon 1 (kek1) as an inhibitor of the epidermal growth factor receptor (EGFR) and demonstrate that it acts in a negative feedback loop to modulate the activity of the EGFR tyrosine kinase. During oogenesis, kek1 is expressed in response to the Gurken/EGFR signaling pathway, and loss of kek1 activity is associated with an increase in EGFR signaling. Consistent with our loss-of-function studies, we demonstrate that ectopic overexpression of kek1 mimics a loss of EGFR activity. We show that the extracellular and transmembrane domains of Kek1 can inhibit and physically associate with the EGFR, suggesting potential models for this inhibitory mechanism.

Original languageEnglish (US)
Pages (from-to)847-856
Number of pages10
JournalCell
Volume96
Issue number6
StatePublished - Mar 19 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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