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J. Biol. Chem., Vol. 278, Issue 17, 14978-14984, April 25, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/17/14978    most recent M212118200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, J. Articles by Feldman, R. A. Search for Related Content PubMed PubMed Citation Articles by Kim, J. Articles by Feldman, R. A. Social Bookmarking                      What's this?

Fes Tyrosine Kinase Promotes Survival and Terminal Granulocyte Differentiation of Factor-dependent Myeloid Progenitors (32D) and Activates Lineage-specific Transcription Factors^*

Jynho Kim, Yoshiyasu Ogata, and Ricardo A. Feldman

From the Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201

The c-fps/fes proto-oncogene encodes a 92-kDa protein-tyrosine kinase that is involved in myeloid cell development and function. We have recently shown that expression of an activated allele of Fes (Fes^act) in monocyte precursors resulted in their differentiation into functional macrophages through the activation of lineage-specific transcription factors. We now report that this kinase also plays a role in the survival and terminal differentiation of granulocyte progenitors. The expression of Fes^act in factor-dependent 32D cells prevented their apoptotic death after interleukin-3 removal, but Fes^act-expressing cells remained factor-dependent for proliferation. Removal of interleukin-3 from the Fes^act-expressing cells was followed by granulocytic differentiation in the absence of granulocyte colony-stimulating factor within 4-8 days. The differentiated cells had distinctive granulocyte morphology and there was up-regulation of CD11b, Gr-1, and late differentiation markers such as lactoferrin, suggesting that this kinase induced terminal granulocytic differentiation. Concomitantly, Fes^act down-regulated the macrophage marker F4/80, suggesting that the biological activity of Fes was coordinated in a lineage-specific manner. Further analysis showed that Fes^act caused activation of CCAAT/enhancer-binding protein- and STAT3, two transcription factors that are involved in granulocyte differentiation. Our results provide evidence that Fes may be a key component of the granulocyte differentiation machinery, and suggest a potential mechanism by which this kinase may regulate granulocyte-specific gene expression.

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