Erythropoietin-induced recruitment of Shc via a receptor phosphotyrosine-independent, Jak2-associated pathway.
Based on the recently implicated role of Shc as a signaling effector for type I cytokine receptors, factors which mediate the recruitment and phosphorylation of Shc in the erythropoietin receptor (EPOR) system have been studied. FDC-P1 cells stably expressing the wild type murine EPOR supported the EPO-induced association of Shc with Jak2 and its rapid tyrosine phosphorylation. However, this did not depend upon the presence of phosphotyrosine sites within the EPOR and was mediated by a mitogenically deficient receptor form (EPOR329) lacking cytoplasmic tyrosine residues. This was shown both by Western blotting of Shc and Jak2 co-immunoprecipitates and through the development of an in vitro assay for cytokine-induced Shc phosphorylation. The direct association of Shc with Jak2 also was observed and was shown to depend upon EPO-exposure and the SH2 subdomain of Shc. Together, these studies indicate that Jak2, in part, may mediate the EPO-induced phosphorylation of Shc.
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Department of Biochemistry & Molecular Biology, Pennsylvania State University, University Park 16802, USA.
Jiang
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Zhuang
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Wojchowski
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D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D053614:Janus Kinase 2; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019000:Phosphotyrosine; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D017931:DNA Primers; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D019000:Phosphotyrosine; D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D053614:Janus Kinase 2