To phosphorylate or not to phosphorylate: Selective alterations in tyrosine kinase-inhibited EphB mutant mice

Abstract

EphB tyrosine kinase receptors have been implicated in multiple developmental processes; however, the signaling mechanism underlying these events remains unclear. Through a triple knock-in mouse line for three neurally expressed EphBs, Sokis et al. demonstrated that EphB tyrosine kinase activity is required for axon guidance but does not influence synapse formation. This short communication highlights their study and appealing molecular approach that elucidated the functions of EphB tyrosine kinase during developmental events.

Keywords: Eph B; PP1 analogue; bidirectional signaling; ephrin; tyrosine kinase.

Figure 1. Schematic representation of AS-EphB triple knock-in mutants compared with WT at both structural and functional levels. (A) Bidirectional signaling by ephrin along with wild-type and analog-sensitive EphB receptors. The ligand and receptor are both phosphorylated. Following EphB receptor binding, tyrosine kinase activity is activated along with other kinase-independent mechanisms, e.g., PDZ domain. However, in mutant Eph B, tyrosine kinase activity is inhibited by PP1 analogues. (B) Roles of EphB tyrosine kinase (TK) activity during developmental events in analog-sensitive EphB triple knock-in mouse line treated with PP1 analogs for specified times. (i) Retinal axon guidance requires EphB receptor tyrosine kinase signaling. In the optic chiasm (OC), there was a reduction in ipsilateral radial glial cells (RGC) projections. (ii) EphB receptor TK signaling regulates corpus callosum formation. Defective corpus callosum formation leads to a gap in dorsal midline region following PP1 analogs treatment. (iii) In the dentate gyrus (DG) of hippocampal slices, Ephrin B receptor TK is not required for synaptogenesis. No differences observed in dendritic spine formation.