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Fibroblast growth factor receptor 2 (FGFR2) in brain neurons and retinal pigment epithelial cells act via stimulation of neuroendocrine L-type channels (Ca_v1.3)

Institut für Klinische Physiologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 12200 Berlin, Germany

¹Correspondence: Institut f. Klinische Physiologie, Universitaetsklinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: strauss{at}ukbf.fu-berlin.de

In contrast to the fibroblast growth factor receptor 1 (FGFR1), little is known about intracellular signaling of FGFR2. The signaling cascade of FGFR2 was studied using the perforated patch configuration of the patch-clamp technique in cultured rat retinal pigment epithelial (RPE) cells that express both FGFR1 and FGFR2. Interaction of signaling proteins was studied using immunoprecipitation techniques with membrane proteins from RPE cells and freshly isolated rat brain. When Ba²⁺ currents through L-type channels were studied, extracellular application of bFGF (10 ng/ml) led to a shift of the steady-state activation to more negative values. In 50% of cells, an additional increase in maximal current amplitude was observed. This effect was blocked by the tyrosine kinase inhibitor lavendustin A (10^-5 M) but was not influenced by the FGFR1 blocker SU5402 (2x10^-5 M) or by the blocker for src-kinase herbimycin A (10^-5 M). Immunoprecipitation of FGFR2 led to coprecipitation of 1D Ca²⁺ channel subunits and precipitation of 1D subunits led to coprecipitation of FGFR2. Immunoprecipitation of FGFR1 did not result in the coprecipitation with 1D Ca²⁺ channel subunits. The coprecipitation results were comparable when using brain tissue and RPE cells. The 1D subunit-specific band were stained with antiphosphotyrosine antibodies. We conclude that FGFR2 acts via a different signaling cascade than FGFR1. This cascade involves an src-kinase-independent, close functional interaction of FGFR2 and the subunit of neuroendocrine L-type channels.—Rosenthal, R., Thieme, H., Strauss, O. Fibroblast growth factor receptor 2 (FGFR2) in brain neurons and retinal pigment epithelial cells act via stimulation of neuroendocrine L-type channels (Ca_v1.3).

Key Words: RPE • bek • flg • Ca²⁺ channels • bFGF

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