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J. Biol. Chem., Vol. 282, Issue 31, 22573-22581, August 3, 2007

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The Early Growth Response Factor-1 Is Involved in Stem Cell Factor (SCF)-induced Interleukin 13 Production by Mast Cells, but Is Dispensable for SCF-dependent Mast Cell Growth^*

Bo Li¹, Jason Berman, Jin-Tian Tang, and Tong-Jun Lin, Supported by a New Investigator Award from the Canadian Institutes of Health Research and an Investigatorship from the Izaak Walton Killam Health Center²

From the Departments of Microbiology and Immunology, and Pediatrics, Izaak Walton Killam Health Center, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada and the Institute of Medical Physics and Engineering, Tsinghua University, Beijing 100084, China

The stem cell factor (SCF) plays a central role in the regulation of mast cell function and growth. However, roles of transcription factors involved in these processes remain incompletely defined. The early growth response factor-1 (Egr-1) is a member of the zinc finger transcription factor family. A role for Egr-1 in SCF-induced mast cell activation and growth was investigated in mouse bone marrow-derived mast cells (BMMC). The stimulation of BMMC with SCF induced a strong expression of Egr-1 mRNA. SCF-induced Egr-1 nuclear translocation and DNA binding were demonstrated by electrophoretic mobility shift assay (EMSA) and immunofluorescence assay. SCF-induced IL-13 expression was significantly reduced at both mRNA and protein levels in Egr-1-deficient BMMC. In addition, the synergy between IgE and SCF on IL-13 and IL-4 production was reduced in Egr-1-deficient mast cells. Interestingly, Egr-1 deficiency had little effect on SCF-induced mast cell growth. SCF-induced Egr activation likely requires tyrosine phosphorylation because a tyrosine kinase inhibitor PP2 blocked SCF-induced nuclear protein binding to Egr probe as determined by EMSA. Thus, Egr-1 is required for SCF-induced IL-13 expression, but not mast cell growth. Egr-1 represents a novel mechanism for SCF-induced mast cell activation.

Received for publication, November 24, 2006 , and in revised form, June 4, 2007.

^* This work was supported by grants from the Canadian Institutes of Health Research, Nova Scotia Health Research Foundation, and Izaak Walton Killam Health Center (to T. J. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S6.

¹ Current address: Inst. of Medical Physics and Engineering, Tsinghua University, Beijing 100084, China.

² To whom correspondence should be addressed: IWK Health Center, Dept. of Pediatrics, 5850 University Ave., Halifax, NS B3K 6R8, Canada. Tel.: 902-470-8834; Fax: 902-470-7812; E-mail: tong-jun.lin{at}dal.ca.

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