RYK, a catalytically inactive receptor tyrosine kinase, associates with EphB2 and EphB3 but does not interact with AF-6.
RYK is an atypical orphan receptor tyrosine kinase that lacks detectable kinase activity. Nevertheless, using a chimeric receptor approach, we previously found that RYK can signal via the mitogen-activated protein kinase pathway. Recently, it has been shown that murine Ryk can bind to and be phosphorylated by the ephrin receptors EphB2 and EphB3. In this study, we show that human RYK associates with EphB2 and EphB3 but is not phosphorylated by them. This association requires both the extracellular and cytoplasmic domains of RYK and is not dependent on activation of the Eph receptors. It was also previously shown that AF-6 (afadin), a PDZ domain-containing protein, associates with murine Ryk. We show here that AF-6 does not bind to human RYK in vitro or in vivo. This suggests that there are significant functional differences between human and murine RYK. Further studies are required to determine whether RYK modulates the signaling of EphB2 and EphB3.
Trivier
Elisabeth
E
Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom.
Ganesan
Trivadi S
TS
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D036183:Receptor, EphB2; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D036081:Receptors, Eph Family; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013379:Substrate Specificity; D014162:Transfection
C095516:AFDN protein, human; D011956:Receptors, Cell Surface; C080836:RYK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036183:Receptor, EphB2; D036081:Receptors, Eph Family; D009218:Myosins; D016547:Kinesins