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.
Ghiglione
C
C
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Carraway
K L
KL
Amundadottir
L T
LT
Boswell
R E
RE
Perrimon
N
N
Duffy
J B
JB
D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins; D066246:ErbB Receptors / Q000378:metabolism*; D005246:Feedback; D015870:Gene Expression; D019476:Insect Proteins / Q000378:metabolism*; D048369:MAP Kinase Kinase 1; D008565:Membrane Proteins / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009866:Oogenesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha; D015291:Transforming Growth Factors / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016211:Transforming Growth Factor alpha; C083730:grk protein, Drosophila; D015291:Transforming Growth Factors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; C105053:Kek1 protein, Drosophila; D017027:Protein Tyrosine Phosphatases; D018631:ras Proteins