Harmer Nicholas J, Robinson Christopher J, Adam Lucy E, Ilag Leopold L, Robinson Carol V, Gallagher John T, Blundell Tom L
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
Biochem J. 2006 Feb 1;393(Pt 3):741-8. doi: 10.1042/BJ20050985.
The minimal signalling unit for tyrosine kinase receptors is two protomers dimerized by one or more ligands. However, it is clear that maximal signalling requires the formation of larger complexes of many receptors at discrete foci on the cell surface. The biological interactions that lead to this are likely to be diverse and have system specific components. In the present study, we demonstrate that, in the FGF (fibroblast growth factor)-FGFR (FGF receptor) system, multimers of the minimal complex composed of two FGF1 and two FGFR2 protomers can form on a single chain of the co-receptor heparin. Using size-exclusion chromatography, we show that two complexes can form on heparin chains as small as 16 saccharide units. We also show by MS that discrete complexes containing exactly two copies of the minimal signalling unit are formed. However, the doublet of complexes appears to be less co-operative than the formation of the 2:2:1 FGF1:FGFR2:heparin complex, suggesting that this mechanism is one of a number of weaker interactions that might be involved in the formation of a focal complex on the cell surface.
酪氨酸激酶受体的最小信号传导单位是由一个或多个配体二聚化的两个原聚体。然而，很明显，最大信号传导需要在细胞表面离散位点形成由许多受体组成的更大复合物。导致这种情况的生物学相互作用可能多种多样，并具有系统特异性成分。在本研究中，我们证明，在FGF（成纤维细胞生长因子）-FGFR（FGF受体）系统中，由两个FGF1和两个FGFR2原聚体组成的最小复合物的多聚体可以在共受体肝素的单链上形成。使用尺寸排阻色谱法，我们表明，在小至16个糖单元的肝素链上可以形成两个复合物。我们还通过质谱表明形成了恰好包含两个最小信号传导单位拷贝的离散复合物。然而，复合物的双峰似乎比2:2:1 FGF1:FGFR2:肝素复合物的形成协同性更低，这表明该机制是可能参与细胞表面焦点复合物形成的许多较弱相互作用之一。
