title: Mouse FLRT2 interacts with the extracellular and intracellular regions of FGFR2.
abstract: Fibroblast Growth Factor (FGF) signaling is known to be critical in mediating key developmental events during craniofacial development. Recent evidence suggests that members of the Fibronectin (F) Leucine (L) Rich (R) Transmembrane (T), FLRT, family modulate FGF signaling. FLRT2 has a highly specific pattern of expression during craniofacial development, in close relationship with FGFR2. We therefore characterized FLRT2/FGFR2 interactions in the context of craniofacial development and showed, by co-immunoprecipitation and GST pulldown assays with embryonic craniofacial tissue lysates, that FLRT2 interacted with FGFR2. Yeast two-hybrid assays further showed that the intracellular regions of both proteins interacted in addition to the interactions in the extracellular portions. The extracellular Leucine Rich Repeats domain of FLRT2 contributed to the interactions with the extracellular regions of FGFR2. Interactions in the intracellular regions of the 2 proteins were mediated by the C-tail domain in FLRT2. Furthermore, cells stably transfected with FLRT2 shRNAs or FLRT2 cDNA exhibited a concomitant decrease and increase, respectively, in FGFR2 protein, mRNA, and ERK phosphorylation levels, suggesting a positive feedback regulatory loop of FLRT2 on FGF signaling in craniofacial tissues. We propose that FLRT2-FGFR2 interactions represent a potential mechanism for regulation of FGF signaling by FLRT2 during craniofacial development.
authors.affiliation: Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, Canada, M5G 1G6.
authors.forename: K
authors.initials: K
authors.lastname: Wei
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Tse
authors.forename: M F
authors.initials: MF
authors.lastname: Manolson
authors.forename: S-G
authors.initials: SG
authors.lastname: Gong
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004843:Epistasis, Genetic; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D020935:MAP Kinase Signaling System; D008445:Maxillofacial Development; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: C514259:FLRT2 protein, mouse; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048049:Extracellular Signal-Regulated MAP Kinases