Frs2α and Shp2 signal independently of Gab to mediate FGF signaling in lens development

Hongge Li, Chenqi Tao, Zhigang Cai, Kristina Hertzler-Schaefer, Tamica N. Collins, Fen Wang, Gen Sheng Feng, Noriko Gotoh, Xin Zhang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Fibroblast growth factor (FGF) signaling requires a plethora of adaptor proteins to elicit downstream responses, but the functional significances of these docking proteins remain controversial. In this study, we used lens development as a model to investigate Frs2α and its structurally related scaffolding proteins, Gab1 and Gab2,in FGF signaling. We show that genetic ablation of Frs2α alone has a modest effect, but additional deletion of tyrosine phosphatase Shp2 causes a complete arrest of lens vesicle development. Biochemical evidence suggests that this Frs2α-Shp2 synergy reflects their epistatic relationship in the FGF signaling cascade, as opposed to compensatory or parallel functions of these two proteins. Genetic interaction experiments further demonstrate that direct binding of Shp2 to Frs2α is necessary for activation of ERK signaling, whereas constitutive activation of either Shp2 or Kras signaling can compensate for the absence of Frs2α in lens development. By contrast, knockoutof Gab1 and Gab2 failed to disrupt FGF signaling in vitro and lens development in vivo. These results establish the Frs2α-Shp2 complex as the key mediator of FGF signaling in lens development.

Original languageEnglish (US)
Pages (from-to)571-582
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number3
DOIs
StatePublished - Feb 1 2014

Keywords

  • Fgf
  • Frs2
  • Gab
  • Lens
  • Ras
  • Shp2

ASJC Scopus subject areas

  • Cell Biology

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