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Pawson, Tony >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/9444

Title: Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands
Authors: Holland, Sacha J.
Gale, Nicholas W.
Mbamalu, Geraldine
Yancopoulos, George D.
Henkemeyer, Mark
Pawson, Tony
Keywords: DNA-Binding Proteins
Signal Transduction
Transcription Factors
Ephrin-B2
Coculture Techniques
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 [8], 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 [12]. 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 [6]. 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 [18]. 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.
URI: http://www.nature.com/nature/index.html
http://hdl.handle.net/1807/9444
Appears in Collections:Pawson, Tony
Pawson, Tony

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