title: An FGFR1-SPRY2 Signaling Axis Limits Basal Cell Proliferation in the Steady-State Airway Epithelium.
abstract: The steady-state airway epithelium has a low rate of stem cell turnover but can nevertheless mount a rapid proliferative response following injury. This suggests a mechanism to restrain proliferation at steady state. One such mechanism has been identified in skeletal muscle in which pro-proliferative FGFR1 signaling is antagonized by SPRY1 to maintain satellite cell quiescence. Surprisingly, we found that deletion of Fgfr1 or Spry2 in basal cells of the adult mouse trachea caused an increase in steady-state proliferation. We show that in airway basal cells, SPRY2 is post-translationally modified in response to FGFR1 signaling. This allows SPRY2 to inhibit intracellular signaling downstream of other receptor tyrosine kinases and restrain basal cell proliferation. An FGFR1-SPRY2 signaling axis has previously been characterized in cell lines in vitro. We now demonstrate an in vivo biological function of this interaction and thus identify an active signaling mechanism that maintains quiescence in the airway epithelium.
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, Wellcome Trust/MRC Stem Cell Institute, Department of Pathology, University of Cambridge, Cambridge CB2 1QN, UK.
authors.forename: Gayan I
authors.initials: GI
authors.lastname: Balasooriya
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, Wellcome Trust/MRC Stem Cell Institute, Department of Pathology, University of Cambridge, Cambridge CB2 1QN, UK.
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: M Albert
authors.initials: MA
authors.lastname: Basson
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, Wellcome Trust/MRC Stem Cell Institute, Department of Pathology, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: e.rawlins@gurdon.cam.ac.uk.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Rawlins
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse