Identification of EPS8 as a Dvl1-associated molecule.
Dishevelled (Dsh) is involved in both Wingless (Wg) and Frizzled (Fz) signaling pathways. To further determine the function of Dsh, we have performed yeast two-hybrid screening and isolated several genes encoding the molecules associated with the PDZ domain of Dvl1, one of the murine Dsh homologs. During the screening, we found that EPS8, which is a substrate for activated EGF receptor (EGFR), specifically interacted with Dvl1. This interaction was also confirmed in vitro. Through transfection studies, we observed the mutual action between Dvl1 and EPS8. Dvl1 was hyperphosphorylated in the presence of EPS8, whereas the tyrosine phosphorylation of EPS8 by activated EGFR was inhibited in the presence of Dvl1. Immunohistochemistry showed that Dvl1 and EPS8 expression overlap in particular tissues during organogenesis. These results indicate that interaction between Dvl1 and receptor tyrosine kinase signal plays certain roles in developmental events.
Inobe
M
M
Department of Molecular Genetics, National Institute of Neuroscience, Kodaira, Tokyo, 187-8502, Japan.
Katsube
K i
Ki
Miyagoe
Y
Y
Nabeshima
Y i
Yi
Takeda
S
S
D000135:Acid Phosphatase / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D003598:Cytoskeletal Proteins; D000072261:Dishevelled Proteins; D005314:Embryonic and Fetal Development; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D009928:Organ Specificity; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; C083430:Eps8 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000135:Acid Phosphatase