ARK-1 inhibits EGFR signaling in C. elegans.
A screen for synthetic enhancers of sli-1 identified ark-1 (forAck-related tyrosine kinase), a novel inhibitor of let-23 EGFR signaling in C. elegans. An ark-1 mutation synergizes with mutations in other negative regulators of let-23, resulting in increased RAS signaling. Genetic analysis suggests that ARK-1 acts upstream of RAS and is dependent upon SEM-5. ARK-1 inhibits LET-23-mediated ovulation, a RAS-independent function. ARK-1 physically interacts with SEM-5 in the yeast two-hybrid assay. We find that sem-5 also has a negative function in let-23-mediated ovulation and suggest that this negative function is mediated by the recruitment of inhibitors such as ARK-1.
Hopper
N A
NA
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom. nah@mrc-lmb.cam.ac.uk
Lee
J
J
Sternberg
P W
PW
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000502:physiology; D017238:Genes, Helminth; D005804:Genes, Lethal; D011905:Genes, ras; D015801:Helminth Proteins / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010060:Ovulation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D014844:Vulva / Q000254:growth & development
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C412505:Ack-related tyrosine kinase-1, C elegans; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C085873:let-23 protein, C elegans