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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0271. This Article Full Text (PDF) All Versions of this Article: 2001-12-0271v1 99/11/4030    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by ZHOU, Q. Articles by SIMS, P. J Search for Related Content PubMed PubMed Citation Articles by ZHOU, Q. Articles by SIMS, P. J Social Bookmarking                   What's this? Submitted December 19, 2001 Accepted February 5, 2002 Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1 QUANSHENG ZHOU, JI ZHAO, THERESE WIEDMER, and PETER J SIMS* MOLECULAR & EXPERIMENTAL MEDICINE, THE SCRIPPS RESEARCH INSTITUTE, LA JOLLA, CA, USA MOLECULAR & EXPERIMENTAL MEDICINE, THE SCRIPPS RESEARCH INSTITUTE, LA JOLLA, CA, USA; VASCULAR BIOLOGY, THE SCRIPPS RESEARCH INSTITUTE, LA JOLLA, CA, USA * Corresponding author; email: psims{at}scripps.edu. Phospholipid scramblase 1 (PLSCR1) is an endofacial plasma membrane protein proposed to participate in transbilayer movement of phosphatidylserine and other phospholipids. In addition to its putative role in the reorganization of plasma membrane phospholipids, PLSCR1 is a substrate of intracellular kinases that imply its possible participation in diverse signaling pathways underlying proliferation, differentiation, or apoptosis. As PLSCR1 is prominently expressed in a variety of blood cells, we evaluated phospholipid scramblase activity in platelets and erythrocytes, and cytokine-dependent growth of hematopoietic precursor cells, of PLSCR1 knockout mice. Adult PLSCR1-/- mice showed no obvious hematologic or hemostatic abnormality, and blood cells from these animals normally mobilized phosphatidylserine to the cell surface upon stimulation. Whereas blood cell counts in adult PLSCR1-/-mice were normal, in both fetus and newborn animals, neutrophil counts were significantly depressed relative to age-matched wild-type (WT). Furthermore, when compared to WT, hematopoietic precursor cells from PLSCR1-/- mice showed defective colony formation and impaired differentiation to mature granulocytes as stimulated by SCF and G-CSF. By contrast, PLSCR1-/- cells showed normal colony formation stimulated by IL3 or GM-CSF, and expansion of megakaryocytic and erythroid progenitors by thrombopoietin or erythropoietin were unaffected. SCF and G-CSF were also found to induce marked increases in PLSCR1 levels in WT cells. Consistent with in vitro assays, PLSCR1-/- mice treated with G-CSF showed <50% of the granulocytosis observed in identically treated WT mice. These data provide direct evidence that PLSCR1 functionally contributes to cytokine-regulated cell proliferation and differentiation, and suggest it is required for normal myelopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Huett, A. Ng, Z. Cao, P. Kuballa, M. Komatsu, M. J. Daly, D. K. Podolsky, and R. J. Xavier A Novel Hybrid Yeast-Human Network Analysis Reveals an Essential Role for FNBP1L in Antibacterial Autophagy J. Immunol., April 15, 2009; 182(8): 4917 - 4930. 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