Tyrosine phosphorylation of transmembrane ligands for Eph receptors.
Axonal pathfinding in the nervous system is mediated in part by cell-to-cell signaling events involving members of the Eph receptor tyrosine kinase (RTK) family and their membrane-bound ligands. Genetic evidence suggests that transmembrane ligands may transduce signals in the developing embryo. The cytoplasmic domain of the transmembrane ligand Lerk2 became phosphorylated on tyrosine residues after contact with the Nuk/Cek5 receptor ectodomain, which suggests that Lerk2 has receptorlike intrinsic signaling potential. Moreover, Lerk2 is an in vivo substrate for the platelet-derived growth factor receptor, which suggests crosstalk between Lerk2 signaling and signaling cascades activated by tyrosine kinases. It is proposed that transmembrane ligands of Eph receptors act not only as conventional RTK ligands but also as receptorlike signaling molecules.
Brückner
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K
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. USA.
Pasquale
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EB
Klein
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D016475:3T3 Cells; D000818:Animals; D001369:Axons / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D036387:Ephrin-B1; D008024:Ligands; D051379:Mice; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020801:Receptor, Ciliary Neurotrophic Factor; D036183:Receptor, EphB2; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D036387:Ephrin-B1; D008024:Ligands; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; C586311:Ephb2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D036183:Receptor, EphB2; D017479:Receptors, Platelet-Derived Growth Factor