divergent pathways in cos-7 cells mediate defective internalization and intracellular routing of truncated g-csfr forms in scnaml发散cos-7细胞通路调节缺陷内化和细胞内路由scnaml截断g-csfr形式.pdfVIP

Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G- CSFR Forms in SCN/AML 1,2 3 4 5 6 Melissa G. Hunter , Morgan McLemore , Daniel C. Link , Megan Loveland , Alexander Copelan , Belinda R. Avalos2,5* 1 Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, Ohio, United States of America, 2 Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America, 3 Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, United States of America, 4 Division of Bone Marrow Transplantation and Stem Cell Biology, Washington University, St. Louis, Missouri, United States of America, 5 Division of Hematology/ Oncology, The Ohio State University, Columbus, Ohio, United States of America, 6 Johns Hopkins University, Baltimore, Maryland, United States of America Abstract Background: Expression of truncated G-CSFR forms in patients with SCN/AML induces hyperproliferation and prolonged cell survival. Previously, we showed that ligand internalization is delayed and degradation of truncated G-CSFR forms is defective in patients with SCN/AML. Methodology/Principal Findings: In this study, we investigated the potential roles of dileucine and tyrosine-based motifs within the cytoplasmic domain of the G-CSFR in modulating ligand/receptor internalization. Using standard binding assays with radiolabeled ligand and COS-7 cells, substitutions in the dileucine motif or deletion of tyrosine residues in the G-CSFR did not alter internalization. Attachment of the transferrin receptor YTRF internalization motif to a truncated G-CSFR form from a patient with SCN/AML corrected defect