GROWTH FACTOR RECEPTORS FGF Receptor Gets More Company

Fibroblast growth factor (FGF) regulates many facets of animal development. Proteins that are expressed in the same pattern as FGF and are involved in the same signaling pathway are referred to as the FGF synexpression group and, thus far, include the FGF receptor (FGFR), a transmembrane protein called Sef, intracellular proteins of the sprouty family, and transcription factors such as Erm and Pea3. Sef and sprouty negatively regulate FGF signaling. Böttcher et al. have identified a positive regulatory protein in Xenopus that is a member of the fibronectin-leucine-rich transmembrane protein family (XFLRT3), which may also belong to this synexpression group. The expression of XFLRT3 resembles that of FGF8 in developing Xenopus embryos, and its expression is regulated by FGF. Expression of a dominant-negative form of the FGFR blocked the effect of XFLRT3 on gene expression, and both proteins coimmunoprecipitated when overexpressed in cultured mammalian cells, which suggests an interaction at the plasma membrane. XFLRT3 overexpression also activated the mitogen-activated protein kinase signaling arm of the FGF pathway. The authors propose that XFLRT3 modulates FGF signaling directly or recruits factors to the membrane to enhance signaling. The FGFR may reside with both positive and negative regulators in a large complex at the cell surface.

R. T. Böttcher, N. Pollet, H. Delius, C. Niehrs, The transmembrane protein XFLRT3 forms a complex with FGF receptors and promotes FGF signalling. Nat. Cell Biol. 6, 38-44 (2004). [Online Journal]