Jacobsen Jacob, Kiselyov Vladislav, Bock Elisabeth, Berezin Vladimir
Protein Laboratory, Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Building 24.2, Blegdamsvej 3, 2200, Copenhagen N, Denmark.
Neurochem Res. 2008 Dec;33(12):2532-9. doi: 10.1007/s11064-008-9680-2. Epub 2008 Mar 27.
The mechanism of fibroblast growth factor receptor (FGFR) activation by the neural cell adhesion molecule (NCAM) is not well understood. A motif in the second NCAM fibronectin type III (FN3) module, termed FGL, has by means of nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) analyses been demonstrated to be involved in NCAM-FGFR interactions. An FGFR activation motif (FRM) in the first NCAM FN3 module also has been suggested to take part in NCAM interactions with FGFR. Here, we show for the first time that a peptide motif in the second NCAM FN3 module, different from the previously described FGL motif (NLIKQDDGGSPIRHY; termed BCL) binds and activates FGFR and induces FGFR-dependent neurite outgrowth in cultures of cerebellar granule neurons. Our results provide evidence that the BCL motif is one of the multiple FGFR binding sites in NCAM.
神经细胞黏附分子(NCAM)激活成纤维细胞生长因子受体(FGFR)的机制尚未完全明确。NCAM第二个纤连蛋白III型(FN3)结构域中的一个基序,称为FGL,通过核磁共振(NMR)和表面等离子体共振(SPR)分析已被证明参与NCAM与FGFR的相互作用。NCAM第一个FN3结构域中的一个FGFR激活基序(FRM)也被认为参与了NCAM与FGFR的相互作用。在此,我们首次表明,NCAM第二个FN3结构域中的一个肽基序,不同于先前描述的FGL基序(NLIKQDDGGSPIRHY;称为BCL),可结合并激活FGFR,并在小脑颗粒神经元培养物中诱导FGFR依赖性神经突生长。我们的结果提供了证据,证明BCL基序是NCAM中多个FGFR结合位点之一。