Cloning of a novel phosphotyrosine binding domain containing molecule, Odin, involved in signaling by receptor tyrosine kinases

Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Oncogene (Impact Factor: 8.46). 12/2002; 21(52):8029-36. DOI: 10.1038/sj.onc.1205988
Source: PubMed


We have used a proteomic approach using mass spectrometry to identify signaling molecules involved in receptor tyrosine kinase signaling pathways. Using affinity purification by anti-phosphotyrosine antibodies to enrich for tyrosine phosphorylated proteins, we have identified a novel signaling molecule in the epidermal growth factor receptor signaling pathway. This molecule, designated Odin, contains several ankyrin repeats, two sterile alpha motifs and a phosphotyrosine binding domain and is ubiquitously expressed. Using antibodies against endogenous Odin, we show that it undergoes tyrosine phosphorylation upon addition of growth factors such as EGF or PDGF but not by cytokines such as IL-3 or erythropoietin. Immunofluorescence experiments as well as Western blot analysis on subcellular fractions demonstrated that Odin is localized to the cytoplasm both before and after growth factor treatment. Deletion analysis showed that the phosphotyrosine binding domain of Odin is not required for its tyrosine phosphorylation. Overexpression of Odin, but not an unrelated adapter protein, Grb2, inhibited EGF-induced activation of c-Fos promoter. Microinjection of wild-type or a mutant version lacking the PTB domain into NIH3T3 fibroblasts inhibited PDGF-induced mitogenesis. Taken together, our results indicate that Odin may play a negative role in growth factor receptor signaling pathways.

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Available from: Serge Roche, Mar 04, 2015
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    • "Notably, q-oxPTPome cannot yet identify the PTPs oxidized upon growth factor stimulation, probably because only a small subset of PTPs is inactivated (under steady state conditions) by growth factor-evoked ROS (e.g., see (den Hertog et al., 2005; Rhee et al., 2000; Woo et al., 2010)). Similar obstacles confronted initial phosphoproteomic (including pY-proteomic) methods, prior to secondary enrichment strategies (Ahn et al., 2007; Pandey et al., 2002). "
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    • "From the marginally characterised pY proteins found by mass spectrometry that are not known SFK substrates, the Odin protein was selected for further experimental investigation. Odin has been first described as a target and signal transmitter of receptor tyrosine kinases like EGFR and PDGFR [22] and more recently as an interaction partner of the receptor tyrosine kinase EphA8 [23]. Odin reduction by siRNA diminishes ephrinA5-induced effects like cell migration in HEK293 cells and neurite retraction in Neuro2a cells. "
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