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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1466-1474. Prepublished online as a Blood First Edition Paper on May 17, 2007; DOI 10.1182/blood-2007-03-079178. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-03-079178v1 110/5/1466    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 Boyle, K. Articles by Robb, L. Search for Related Content PubMed PubMed Citation Articles by Boyle, K. Articles by Robb, L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 12, 2007 Accepted May 6, 2007 The SOCS box of suppressor of cytokine signaling-3 contributes to the control of G-CSF responsiveness in vivo Kristy Boyle, Paul Egan, Steven Rakar, Tracy A Willson, Ian P. Wicks, Donald Metcalf, Douglas J. Hilton, Nicos A. Nicola, Warren S Alexander, Andrew W Roberts, and Lorraine Robb* Department of Medical Biology, University of Melbourne, Parkville, Australia Division of Autoimmunity and Transplantation, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia Zenyth Therapeutics, Richmond, Australia Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia * Corresponding author; email: robb{at}wehi.edu.au. Suppressor of cytokine signaling (SOCS)-3 is a negative regulator of granulocyte-colony stimulating factor (G-CSF) signaling in vivo. SOCS proteins regulate cytokine signaling by binding, via their SH2 domains, to activated cytokine receptors or their associated Janus kinases. In addition, they bind to the elongin B/C ubiquitin ligase complex via the SOCS box. To ascertain the contribution of the SOCS box of SOCS3 to in vivo regulation of G-CSF signaling, we generated mice expressing a truncated SOCS3 protein lacking the C-terminal SOCS box (SOCS3SB/SB). SOCS3SB/SB mice were viable, had normal steady-state hematopoiesis and did not develop inflammatory disease. Despite their mild phenotype, STAT3 activation in response to G-CSF signaling was prolonged in SOCS3SB/SB bone marrow. SOCS3SB/SB bone marrow contained increased numbers of colony forming cells responsive to G-CSF and IL-6. Treatment of the mice with pharmacological doses of G-CSF, which mimics emergency granulopoiesis and therapeutic use of G-CSF, revealed that SOCS3SB/SB mice were hyper-responsive to G-CSF. Compared with wild type mice, SOCS3SB/SB mice developed a more florid arthritis when tested using an acute disease model. Overall, the results establish a role for the SOCS box of SOCS3 in the in vivo regulation of G-CSF signaling and the response to inflammatory stimuli. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: SOCS box: fine-tuning inflammatory responses Robert P. Coppes Blood 2007 110: 1403-1404. [Full Text] [PDF] This article has been cited by other articles: K. Miyamoto, T. Miyamoto, R. Kato, A. Yoshimura, N. Motoyama, and T. Suda FoxO3a regulates hematopoietic homeostasis through a negative feedback pathway in conditions of stress or aging Blood, December 1, 2008; 112(12): 4485 - 4493. [Abstract] [Full Text] [PDF]

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