Sprouty2-modulated Kras signaling rescues Shp2 deficiency during lens and lacrimal gland development
| Autor: | Xin Zhang, Andrea Powers, Yi Pan, Christian Carbe, Gen-Sheng Feng |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Protein Tyrosine Phosphatase
Non-Receptor Type 11 Lacrimal gland Protein tyrosine phosphatase Protein Serine-Threonine Kinases Biology Lacrimal apparatus medicine.disease_cause Proto-Oncogene Proteins p21(ras) Mice Lens Crystalline medicine Animals Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases Molecular Biology Research Articles Adaptor Proteins Signal Transducing Mice Knockout Intracellular Signaling Peptides and Proteins Lacrimal Apparatus Membrane Proteins Cell cycle Crystallins Cell biology Phenotype medicine.anatomical_structure KRAS Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction Developmental Biology |
| Zdroj: | Development. 137:1085-1093 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.042820 |
| Popis: | Shp2/Ptpn11 tyrosine phosphatase is a general regulator of the RTK pathways. By genetic ablation, we demonstrate that Shp2 is required for lacrimal gland budding, lens cell proliferation, survival and differentiation. Shp2 deletion disrupted ERK signaling and cell cycle regulation, which could be partially compensated by activated Kras signaling, confirming that Ras signaling was the main downstream target of Shp2 in lens and lacrimal gland development. We also showed that Sprouty2, a general suppressor of Ras signaling, was regulated by Shp2 positively at the transcriptional level and negatively at the post-translational level. Only in the absence of Sprouty2 could activated Kras signaling robustly rescue the lens proliferation and lacrimal-gland-budding defects in the Shp2 mutants. We propose that the dynamic regulation of Sprouty by Shp2 might be important not only for modulating Ras signaling in lens and lacrimal gland development, but also for RTK signaling in general. |
| Databáze: | OpenAIRE |
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