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

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.

Pubmed ID: 10102272


  • Ghiglione C
  • Carraway KL
  • Amundadottir LT
  • Boswell RE
  • Perrimon N
  • Duffy JB



Publication Data

March 19, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA71702

Mesh Terms

  • Animals
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Drosophila
  • Drosophila Proteins
  • Feedback
  • Gene Expression
  • Insect Proteins
  • MAP Kinase Kinase 1
  • Membrane Proteins
  • Mitogen-Activated Protein Kinase Kinases
  • Nerve Tissue Proteins
  • Oogenesis
  • Protein Tyrosine Phosphatases
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-raf
  • Receptor, Epidermal Growth Factor
  • Signal Transduction
  • Transforming Growth Factor alpha
  • Transforming Growth Factors
  • ras Proteins