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Molecular and Cellular Biology, December 2004, p. 10584-10592, Vol. 24, No. 24
0270-7306/04/$08.00+0 DOI: 10.1128/MCB.24.24.10584-10592.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Interplay between MITF, PIAS3, and STAT3 in Mast Cells and Melanocytes
Amir Sonnenblick,
Carmit Levy,
and
Ehud Razin*
Department of Biochemistry, Hebrew University, Hadassah Medical School, Jerusalem, Israel
Received 21 April 2004/
Returned for modification 16 June 2004/
Accepted 13 September 2004
Microphthalmia transcription factor (MITF) and STAT3 are two transcription factors that play a major role in the regulation of growth and function in mast cells and melanocytes. In the present study, we explored the MITF-PIAS3-STAT3 network of interactions, how these interactions regulate gene expression, and how cytokine-mediated phosphorylation of MITF and STAT3 is involved in the in vivo interplay between these three proteins. In NIH 3T3 cells stimulated via gp130 receptor, transfected MITF was found to be phosphorylated at S409. Such phosphorylation of MITF leads to PIAS3 dissociation from MITF and its association with STAT3. Activation of mouse melanoma and mast cells through gp130 or c-Kit receptors induced the mobilization of PIAS3 from MITF to STAT3. In mast cells derived from MITFdi/di mice, whose MITF lacks the Zip domain (PIAS3-binding domain), we found downregulation in mRNA levels of genes regulated by either MITF or STAT3. This regulatory mechanism is of considerable importance since it is likely to advance the deciphering of a role for MITF and STAT3 in mast cells and melanocytes.
* Corresponding author. Mailing address: Department of Biochemistry, Hebrew University Hadassah Medical School, POB 12272, Jerusalem 91120, Israel. Phone: 972-2-675-8288. Fax: 972-2-675-8986. E-mail: ehudr{at}cc.huji.ac.il.
A.S. and C.L. contributed equally to this study.
Molecular and Cellular Biology, December 2004, p. 10584-10592, Vol. 24, No. 24
0022-538X/04/$08.00+0 DOI: 10.1128/MCB.24.24.10584-10592.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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Copyright © 2004 by the American Society for Microbiology. All rights reserved.