The fibroblast growth factor receptor FGFR-4 acts as a ligand dependent modulator of erythroid cell proliferation

Receptor and non-receptor tyrosine kinases constitute a large family of proteins that play a pivotal role in hematopoiesis. Here we conducted a comprehensive survey of tyrosine kinase gene expression in primary erythroid progenitor cells from bone marrow by employing a PCR-based strategy that targets the conserved kinase encoding region. We demonstrate that erythroid progenitor cells express several receptor and non-receptor tyrosine kinases, like c-kit, Jak1, Ryk, FAK, Syk, Arg, Csk and members of the insulin receptor family. Specific changes in the expression profile of tyrosine kinases were observed following differentiation induction. We also report on the identification of a new ligand dependent modulator of erythropoiesis, fibroblast growth factor receptor-4 (FGFR-4). FGFR-4 is effectively expressed in erythroid progenitors and downregulated when cells differentiate. Furthermore, the FGFR-4 ligand, basic fibroblast growth factor (bFGF), enhanced erythroid cell proliferation induced by SCF or insulin, and thus modulated both erythroid proliferation and differentiation in vitro.