Ephrin signaling

The interaction between ephrin (EFN) ligands and EPH receptors results not only in forward signaling through the EPH receptor, but also in 'reverse' signaling through the EFN ligand itself. Reverse signaling through EFNB is required for correct spine morphogenesis and proper path-finding of corpus callosum and dorsal retinal axons. The molecular mechanism by which EFNBs transduce a reverse signal involves phosphorylation of multiple, conserved tyrosines on the intracellular domain of B-type ephrins, facilitating binding of the SH2/SH3 domain adaptor protein GRB4 and subsequent cytoskeletal remodeling (Bruckner et al. 1997, Cowan & Henkemeyer 2001, Lu et al. 2001). The other mechanism of reverse signaling involves the C-terminus PSD-95/Dlg/ZO-1 (PDZ)-binding motif of EFNBs which recruits various PDZ domain containing proteins. Phosphorylation and PDZ-dependent reverse signaling by ephrin-B1 have each been proposed to play important roles in multiple contexts in development and disease (Bush & Soriano 2009).

eprin（EFN）配体与EPH受体的相互作用不仅通过EPH受体实现正向信号传导，还通过EFN配体本身实现所谓的‘反向’信号传导。通过EFNB实现的反向信号传导对于正确形成脊髓突触和正确引导胼胝体及视网膜背侧轴突的路径至关重要。EFNBs将反向信号传导转导的分子机制涉及B型eprin胞内域多个保守酪氨酸的磷酸化，从而促进SH2/SH3结构域适配蛋白GRB4的结合以及随后的细胞骨架重塑（Bruckner等人，1997年，Cowan与Henkemeyer，2001年，Lu等人，2001年）。反向信号传导的另一种机制涉及EFNBs的C端PSD-95/Dlg/ZO-1（PDZ）结合基序，该基序募集各种包含PDZ结构域的蛋白质。eprin-B1的磷酸化和PDZ依赖性反向信号传导均被提出在发育和疾病的多重情境中发挥重要作用（Bush与Soriano，2009年）。