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

Cell. 1999 Mar 19;96(6):847-56. doi: 10.1016/s0092-8674(00)80594-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Drosophila Proteins
  • Insect Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Transforming Growth Factor alpha
  • grk protein, Drosophila
  • Transforming Growth Factors
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases
  • MAP Kinase Kinase 1
  • Mitogen-Activated Protein Kinase Kinases
  • Kek1 protein, Drosophila
  • Protein Tyrosine Phosphatases
  • ras Proteins