Interaction of the receptor FGFRL1 with the negative regulator Spred1 |
| |
Authors: | Zhuang Lei Villiger Peter Trueb Beat |
| |
Institution: | a Department of Clinical Research, University of Bern, 3010 Bern, Switzerlandb Department of Rheumatology, University Hospital, 3010 Bern, Switzerland |
| |
Abstract: | FGFRL1 is a member of the fibroblast growth factor receptor family. It plays an essential role during branching morphogenesis of the metanephric kidneys, as mice with a targeted deletion of the Fgfrl1 gene show severe kidney dysplasia. Here we used the yeast two-hybrid system to demonstrate that FGFRL1 binds with its C-terminal, histidine-rich domain to Spred1 and to other proteins of the Sprouty/Spred family. Members of this family are known to act as negative regulators of the Ras/Raf/Erk signaling pathway. Truncation experiments further showed that FGFRL1 interacts with the SPR domain of Spred1, a domain that is shared by all members of the Sprouty/Spred family. The interaction could be verified by coprecipitation of the interaction partners from solution and by codistribution at the cell membrane of COS1 and HEK293 cells. Interestingly, Spred1 increased the retention time of FGFRL1 at the plasma membrane where the receptor might interact with ligands. FGFRL1 and members of the Sprouty/Spred family belong to the FGF synexpression group, which also includes FGF3, FGF8, Sef and Isthmin. It is conceivable that FGFRL1, Sef and some Sprouty/Spred proteins work in concert to control growth factor signaling during branching morphogenesis of the kidneys and other organs. |
| |
Keywords: | ERK extracellular signal-regulated kinase EVH Ena/VASP homology FGF fibroblast growth factor FGFR fibroblast growth factor receptor FGFRL1 FGFR-like protein 1 GFP green fluorescent protein GSH glutathione GST glutathione S-transferase KBD c-Kit binding domain MBP maltose binding protein Sef similar expression to FGF genes Spred Sprouty-related protein with EVH1 domain SPR Sprouty related domain |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|