Interaction between the CheY response regulator and the histidine-containing phosphotransfer (HPt) domain of the ArcB sensory kinase in Escherichia coli

AbstractBacteria have devised sophisticated His–Asp phosphorelay signaling systems for eliciting a variety of adaptive responses to their environment. The histidine-containing phosphotransfer (HPt) domain, found in many signal transduction protein, functions as a mediator of the His–Asp phosphorelay. The ArcB anaerobic sensor of E. coli contains such a HPt domain, although its function is not fully understood. In this study, we provide in vivo and in vitro evidence that the HPt domain is capable of interacting with the CheY receiver, which contains a phospho-accepting aspartate residue

Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

BACKGROUND: We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration. METHODS AND RESULTS: After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity. CONCLUSIONS: Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia