2ckn
NMR Structure of the First Ig Module of mouse FGFR1NMR Structure of the First Ig Module of mouse FGFR1
Structural highlights
FunctionFGFR1_MOUSE Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation (By similarity).[1] [2] [3] [4] [5] [6] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFibroblast growth factor (FGF) receptors (FGFRs) regulate a multitude of cellular processes during embryogenesis and in the adult. The extracellular part of the prototypical FGFR consists of three Ig modules (Ig1 - Ig3), in which Ig2 and Ig3 determine affinity and specificity for FGF and heparin, while the Ig1 module is thought to have a regulatory function. The crystal structures of the Ig2 and Ig3 modules alone and in complex with FGF have previously been reported. The structure of the Ig1 module is unknown, and very little is known about the structural determinants for the regulatory function of this module. We describe here the NMR structure of the Ig1 module of mouse FGFR1. The three-dimensional fold of the module belongs to the intermediate Ig subgroup and can be described as a beta-barrel consisting of two beta-sheets. One sheet is formed by A', G, F, C, and C', and the other by A, B, B', E, and D beta-strands. The overall strand topology of the Ig1 module is similar to that of the Ig2 and Ig3 modules. However, the A/A' loop of the Ig1 module is much longer than that of the Ig2 and Ig3 modules. It contains eight extra residues compared to the Ig3 module, and five extra residues compared to Ig2. NMR structure of the first Ig module of mouse FGFR1.,Kiselyov VV, Bock E, Berezin V, Poulsen FM Protein Sci. 2006 Jun;15(6):1512-5. PMID:16731982[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||