Brambilla R, Brückner K, Orioli D, Bergemann A D, Flanagan J G, Klein R
European Molecular Biology Laboratory, Heidelberg, Germany.
Mol Cell Neurosci. 1996;8(2-3):199-209. doi: 10.1006/mcne.1996.0057.
The Eph family of receptor tyrosine kinases and their cell surface bound ligands have been implicated in a number of developmental processes, including axon pathfinding and fasciculation, as well as patterning in the central nervous system. To better understand the complex signaling events taking place, we have undertaken a comparative analysis of ligand-receptor interactions between a subset of ligands, those that are tethered to the cell surface via a transmembrane domain, and a subset of Eph receptors, the so-called Elk subclass. Based on binding characteristics, receptor autophosphorylation, and cellular transformation assays, we find that the transmembrane-type ligands Lerk2 and Elf2 have common and specific receptors within the Elk subclass of receptors. The common receptors Cek10 and Elk bind and signal in response to Lerk2 and Elf2, whereas the Myk1 receptor is specific for Elf2. Elf2, however, fails to signal through Cek5 in a cellular transformation assay, suggesting that Lerk2 may be the preferred Cek5 ligand in vivo. A recently identified third transmembrane-type ligand, Elf3, specifically, but weakly, binds Cek10 and only induces focus formation when activated by C-terminal truncation. This suggests that the physiological Elf3 receptor may have yet to be identified. Knowledge regarding functional ligand-receptor interactions as presented in this study will be important for the design and interpretation of in vivo experiments, e.g., loss-of-function studies in transgenic mice.
受体酪氨酸激酶的Eph家族及其细胞表面结合配体参与了许多发育过程，包括轴突导向和束状化，以及中枢神经系统的模式形成。为了更好地理解所发生的复杂信号事件，我们对一部分配体（即那些通过跨膜结构域与细胞表面相连的配体）和一部分Eph受体（即所谓的Elk亚类）之间的配体-受体相互作用进行了比较分析。基于结合特性、受体自身磷酸化和细胞转化试验，我们发现跨膜型配体Lerk2和Elf2在受体的Elk亚类中有共同的和特定的受体。共同受体Cek10和Elk对Lerk2和Elf2有结合和信号响应，而Myk1受体对Elf2具有特异性。然而，在细胞转化试验中，Elf2不能通过Cek5发出信号，这表明Lerk2可能是体内Cek5的首选配体。最近鉴定出的第三种跨膜型配体Elf3特异性地但微弱地结合Cek10，并且只有在通过C末端截短激活时才诱导灶形成。这表明生理性的Elf3受体可能尚未被鉴定出来。本研究中所呈现的关于功能性配体-受体相互作用的知识对于体内实验的设计和解释（例如转基因小鼠中的功能丧失研究）将是重要的。
