T-Space at The University of Toronto Libraries >
Mount Sinai Hospital >
Pawson, Tony >
Please use this identifier to cite or link to this item:
|Title: ||Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands|
|Authors: ||Holland, Sacha J.|
Gale, Nicholas W.
Yancopoulos, George D.
|Keywords: ||DNA-Binding Proteins|
Tumor Cells, Cultured
|Issue Date: ||24-Oct-1996|
|Publisher: ||Nature Publishing Group|
|Citation: ||Nature. 1996 Oct 24;383(6602):722-5.|
|Abstract: ||Receptor tyrosine kinases of the EPH class have been implicated in the control of axon guidance and fasciculation [1-7], in regulating cell migration , and in defining compartments in the developing embryo [9-11]. Efficient activation of EPH receptors generally requires that their ligands be anchored to the cell surface, either through a transmembrane (TM) region or a glycosyl phosphatidylinositol (GPI) group . These observations have suggested that EPH receptors can transduce signals initiated by direct cell-cell interaction. Genetic analysis of Nuk, a murine EPH receptor that binds TM ligands, has raised the possibility that these ligands might themselves have a signalling function . Consistent with this, the three known TM ligands have a highly conserved cytoplasmic region, with multiple potential sites for tyrosine phosphorylation [12-17]. Here we show that challenging cells that express the TM ligands Elk-L or Htk-L with the clustered ectodomain of Nuk induces phosphorylation of the ligands on tyrosine, a process that can be mimicked both in vitro and in vivo by an activated Src tyrosine kinase. Co-culture of cells expressing a TM ligand with cells expressing Nuk leads to tyrosine phosphorylation of both the ligand and Nuk. These results suggest that the TM ligands are associated with a tyrosine kinase, and are inducibly phosphorylated upon binding Nuk, in a fashion reminiscent of cytokine receptors . Furthermore, we show that TM ligands, as well as Nuk, are phosphorylated on tyrosine in mouse embryos, indicating that this is a physiological process. EPH receptors and their TM ligands therefore mediate bidirectional cell signalling.|
|Appears in Collections:||Pawson, Tony|
This item is licensed under a Creative Commons License
Items in T-Space are protected by copyright, with all rights reserved, unless otherwise indicated.