Purchase this article with an account.
N Kinkl, JA Sahel, D Hicks; Fibroblast Growth Factor 2 Differentially Induces MEK-dependent and MEK-independent ERK1/2 Activation Pathways in Distinct Populations of Rat Retinal Cells In Vitro . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2726.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine fibroblast growth factor 2 (FGF2)-induced signal transduction pathways in different populations of rat retinal cells in vitro. Methods: Specific antibodies for FGFR-1, -2, -3 and -4, and different FGF-related signaling molecules were used to immunolabel primary cultures of different retinal cells [purified photoreceptors (PR), inner retina (IR)] in vitro. FGF2-induced intracellular signaling in purified PR, IR, and purified Müller glial cells [MGC] was examined using phosphorylation specific antibodies. The MEK inhibitor U0126 was used to block ERK1/2 activation in separate trials. Results: Despite widespread expression of FGFR-1, -2, -3 and -4 as well as FGF-related signaling molecules, FGF2-induced tyrosine phosphorylation was distinct, both in terms of kinetics and induced protein tyrosine phosphorylation, among the culture models. ERK1/2 was activated in PR, IR and MGC. Whereas U0126 treatment completely blocked FGF2-induced ERK1/2 phosphorylation and survival of cultured PR, persistent ERK1/2 phosphorylation was observed in cultured IR and MGC. Furthermore U0126 entirely blocked NGF-induced ERK1/2 activation in cerebral glial cells, as well as FGF2-induced ERK1/2 activation in cerebral glial cells. Conclusion: Despite the general presence of FGFRs and FGF-related signaling molecules, cell type-specific signal transduction pathways exist in the rat retina in vitro, with ERK1/2 representing a common downstream effector. FGF2-induced ERK1/2 activation is entirely mediated by MEK within PR, which is responsible for FGF2-stimulated PR survival. In contrast, IR/MGC possess alternative, cell type and growth factor-specific MEK-independent ERK1/2 activation pathways.
This PDF is available to Subscribers Only