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

• DOI: 10.1242/jcs.134478
• Publication Date: 2013-11-28T03:51:26Z
• Authors: Hongge Li; Chenqi Tao; Zhigang Cai; Kristina Hertzler...; Tamica N. Collins; Fen Wang; Gen-Sheng Feng; Noriko Gotoh; Xin Zhang
• Keywords: 0301 basic medicine; 0303 health sciences; Frs2; Gene Expression Regulation, Developmental; Membrane Proteins; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Eye; Phosphoproteins; Cell Line; Fibroblast Growth Factors; Proto-Oncogene Proteins p21(ras); Lens; Mice; 03 medical and health sciences; Lens, Crystalline; FGF; Animals; Shp2; Gab; Phosphorylation; Extracellular Signal-Regulated MAP Kinases; Ras; Adaptor Proteins, Signal Transducing; Signal Transduction

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