sh2-inositol phosphatase 1 negatively influences early megakaryocyte progenitors早期巨核细胞祖细胞sh2-inositol磷酸酶1产生负面影响.pdfVIP

SH -Inositol Phosphatase 1 Negatively Influences Early 2 Megakaryocyte Progenitors 2. 1,3. 2 1 Lia E. Perez , Caroline Desponts , Nancy Parquet , William G. Kerr * 1 Immunology Program, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, Tampa, Florida, United States of America, 2 Blood and Marrow Transplantation Program, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, Tampa, Florida, United States of America, 3 Department of Chemistry, The Scripps Research Institute, San Diego, California, United States of America Abstract Background: The SH2-containing-5 9inositol phosphatase-1 (SHIP) influences signals downstream of cytokine/chemokine receptors that play a role in megakaryocytopoiesis, including thrombopoietin, stromal-cell-derived-Factor-1/CXCL-12 and interleukin-3. We hypothesize that SHIP might control megakaryocytopoiesis through effects on proliferation of megakaryocyte progenitors (MKP) and megakaryocytes (MK). Methodology and Principal Findings: Herein, we report the megakaryocytic phenotype and MK functional assays of hematopoietic organs of two strains of SHIP deficient mice with deletion of the SHIP promoter/first exon or the inositol phosphatase domain. Both SHIP deficient strains exhibit a profound increase in MKP numbers in bone marrow (BM), spleen and blood as analyzed by flow cytometry (Lin2 + + c-Kit CD41 ) and functional assays (CFU-MK). SHIP deficient MKP display increased phosphorylation of Signal Transducers and Activators of Transcription 3 (STAT-3), protein kinase B (PKB/AKT) and extracellular signal-regulated