title: Fibroblast growth factor receptor-induced phosphorylation of ephrinB1 modulates its interaction with Dishevelled.
abstract: The Eph family of receptor tyrosine kinases and their membrane-bound ligands, the ephrins, have been implicated in regulating cell adhesion and migration during development by mediating cell-to-cell signaling events. The transmembrane ephrinB1 protein is a bidirectional signaling molecule that signals through its cytoplasmic domain to promote cellular movements into the eye field, whereas activation of the fibroblast growth factor receptor (FGFR) represses these movements and retinal fate. In Xenopus embryos, ephrinB1 plays a role in retinal progenitor cell movement into the eye field through an interaction with the scaffold protein Dishevelled (Dsh). However, the mechanism by which the FGFR may regulate this cell movement is unknown. Here, we present evidence that FGFR-induced repression of retinal fate is dependent upon phosphorylation within the intracellular domain of ephrinB1. We demonstrate that phosphorylation of tyrosines 324 and 325 disrupts the ephrinB1/Dsh interaction, thus modulating retinal progenitor movement that is dependent on the planar cell polarity pathway. These results provide mechanistic insight into how fibroblast growth factor signaling modulates ephrinB1 control of retinal progenitor movement within the eye field.
authors.affiliation: Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mood
authors.forename: Gopala
authors.initials: G
authors.lastname: Battu
authors.forename: Yon Ju
authors.initials: YJ
authors.lastname: Ji
authors.forename: Arvinder
authors.initials: A
authors.lastname: Singh
authors.forename: Ira O
authors.initials: IO
authors.lastname: Daar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000072261:Dishevelled Proteins; D036387:Ephrin-B1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D036387:Ephrin-B1; D010750:Phosphoproteins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D014443:Tyrosine