FGFR and PTEN signaling interact during lens development to regulate cell survival. Dev Biol 2016 Feb 15;410(2):150-163
Date
01/15/2016Pubmed ID
26764128Pubmed Central ID
PMC4767529DOI
10.1016/j.ydbio.2015.12.027Scopus ID
2-s2.0-84957852055 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
Lens epithelial cells express many receptor tyrosine kinases (RTKs) that stimulate PI3K-AKT and RAS-RAF-MEK-ERK intracellular signaling pathways. These pathways ultimately activate the phosphorylation of key cellular transcription factors and other proteins that control proliferation, survival, metabolism, and differentiation in virtually all cells. Among RTKs in the lens, only stimulation of fibroblast growth factor receptors (FGFRs) elicits a lens epithelial cell to fiber cell differentiation response in mammals. Moreover, although the lens expresses three different Fgfr genes, the isolated removal of Fgfr2 at the lens placode stage inhibits both lens cell survival and fiber cell differentiation. Phosphatase and tensin homolog (PTEN), commonly known as a tumor suppressor, inhibits ERK and AKT activation and initiates both apoptotic pathways, and cell cycle arrest. Here, we show that the combined deletion of Fgfr2 and Pten rescues the cell death phenotype associated with Fgfr2 loss alone. Additionally, Pten removal increased AKT and ERK activation, above the levels of controls, in the presence or absence of Fgfr2. However, isolated deletion of Pten failed to stimulate ectopic fiber cell differentiation, and the combined deletion of Pten and Fgfr2 failed to restore differentiation-specific Aquaporin0 and DnaseIIβ expression in the lens fiber cells.
Author List
Chaffee BR, Hoang TV, Leonard MR, Bruney DG, Wagner BD, Dowd JR, Leone G, Ostrowski MC, Robinson MLAuthor
Gustavo Leone PhD Senior Associate Dean, Center Director, Professor in the Pathology and Laboratory Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Differentiation
Cell Proliferation
Cell Survival
Lens, Crystalline
MAP Kinase Signaling System
Mice
PTEN Phosphohydrolase
Phosphorylation
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-jun
Receptor, Fibroblast Growth Factor, Type 2
Signal Transduction
Tumor Suppressor Protein p53
