In:
Journal of Cell Science, The Company of Biologists
Abstract:
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 protein Gab1 and Gab2 in FGF signaling. We show that genetic ablation of Frs2α alone has 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 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 activating ERK signaling, while constitutive activation of either Shp2 or Kras signaling can compensate for the absence of Frs2α in lens development. In contrast, knockouts of Gab1 and Gab2 failed to disrupt FGF signaling in vitro and lens development in vivo. These results establish Frs2α-Shp2 complex as the key mediator of FGF signaling in lens development.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2013
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
