Granulocytes serve a critical function in host organisms by recognizing and destroying invading microbes, as well as propagating and maintaining inflammation at sites of infection. However, the molecular pathways underpinning the development of granulocytes are poorly understood. Here, we identify a role for CaMKK2 in the restriction of granulocytic fate commitment and differentiation of myeloid progenitor cells. Following BMT, engraftment by Camkk2 −/− donor cells resulted in the increased production of mature granulocytes in the BM and peripheral blood. Similarly, Camkk2 −/− mice possessed elevated numbers of CMP cells and exhibited an accelerated granulopoietic phenotype in the BM. Camkk2 −/− myeloid progenitors expressed increased levels of C/EBPα and PU.1 and preferentially differentiated into Gr1 + Mac1 + granulocytes and CFU-G in vitro. During normal granulopoiesis in vivo or G-CSF-induced differentiation of 32D myeloblast cells in vitro, CaMKK2 mRNA and protein were decreased as a function of time and were undetectable in mature granulocytes. Expression of ectopic CaMKK2 in Camkk2 −/− CMPs was sufficient to rescue aberrant granulocyte differentiation and when overexpressed in 32D cells, was also sufficient to impede granulocyte differentiation in a kinase activity-dependent manner. Collectively, our results reveal a novel role for CaMKK2 as an inhibitor of granulocytic fate commitment and differentiation in early myeloid progenitors. myelopoiesis myeloid progenitors calcium-calmodulin-dependent kinases Footnotes The online version of this paper, found at www.jleukbio.org , includes supplemental information. 32D 32D Clone 3 AMPK AMP-activated protein kinase APC allophycocyanin BM bone marrow BMT bone marrow transplantation CFU-M/G monocyte/macrophage/granulocyte CFU CKLiK CaMKI-like kinase CLP common lymphoid progenitor CMP common myeloid progenitor GMP granulocyte-monocyte progenitor HSC hematopoietic stem cell KLS c-Kit + Sca1 + Lin –/lo Lin lineage MEP megakaryocyte-erythroid progenitor MPP multipotent progenitor p phospho qRT-PCR quantitative RT-PCR rm recombinant mouse Sca-1 stem cell antigen 1 SCF stem cell factor shRNA small hairpin RNA Received March 18, 2011. Revision received June 28, 2011. Accepted July 19, 2011. © 2011 Society for Leukocyte Biology Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print August 4, 2011 , doi: 10.1189/jlb.0311152 November 2011 Journal of Leukocyte Biology vol. 90 no. 5 897-909 » Abstract Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: jlb.0311152v1 90/5/897 most recent Classifications Cell Development, Differentiation, and Trafficking Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Teng, E. C. Articles by Means, A. R. PubMed PubMed citation Articles by Teng, E. C. Articles by Means, A. R. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue November 2011, 90 (5) From the Cover Editorials: Switching on arginase in M2 macrophages. Editorials: Neutrophil apoptosis: hot on the TRAIL of inflammatory resolution. Spotlight on leading Edge Research: Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function. Spotlight on leading Edge Research: TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation. Reviews: Nuocytes: expanding the innate cell repertoire in type-2 immunity. Reviews: Regulation of angiostatic chemokines driven by IL-12 and IL-27 in human tumors. Reviews: Lung dendritic cells at the innate-adaptive immune interface. Technical Advance: Langerhans cells derived from a human cell line in a full-thickness skin equivalent undergo allergen-induced maturation and migration. Alert me to new issues of Journal of Leukocyte Biology About JLB Submit Manuscripts Instructions for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Advertising Press Room Copyright Permissions Feedback Join SLB SLB Annual Meeting Copyright © 2011 by the Society for Leukocyte Biology Print ISSN: 0741-5400 Online ISSN: 1938-3673 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23108860-1"); pageTracker._trackPageview();

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