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Cellular and Molecular Life Sciences: CMLS logoLink to Cellular and Molecular Life Sciences: CMLS
. 2009 Apr 14;66(11-12):1962–1973. doi: 10.1007/s00018-009-8775-5

Regulation of megakaryocytic differentiation of K562 cells by FosB, a member of the Fos family of AP-1 transcription factors

J-K Limb 1,2, S Yoon 1,3, K E Lee 1, B-H Kim 1,3, S Lee 1,3, Y S Bae 1, G-J Jhon 2,, J Kim 1,3,
PMCID: PMC11115838  PMID: 19381435

Abstract.

The regulation of megakaryocytic differentiation is poorly understood. Using K562 cells, which can partly recapitulate the process in response to phorbol 12-myristate 13-acetate (PMA), we performed microarray-based gene expression profiling to identify genes that play significant roles in megakaryopoiesis. Here, we describe the function of FosB, an AP-1 transcription factor. FosB is induced in PMA treated K562 cells in a sustained manner and forms an active AP-1 protein-DNA complex. Down-regulation of FosB with specific shRNAs inhibited the induction of CD41, a specific cell surface marker of megakaryocytes. We also show that activation of the PKC-MEK-ERK signaling pathway is required for induction of FosB and CD41. Finally, we cross-examined the microarray data in conjunction with gene function annotation data to identify additional target genes of FosB. We define 3 genes, INHBA, CD9, and ITGA2B as regulatory targets of FosB and show that CD9, in particular, is a direct target of FosB.

Electronic supplementary material

The online version of this article (doi:10.1007/s00018-009-8775-5) contains supplementary material, which is available to authorized users.

Keywords. FosB, AP-1, megakaryocyte, CD41, K562

Electronic Supplementary material

Below are the links to the electronic supplementary material.

18_2009_8775_MOESM1_ESM.xls (6MB, xls)

Supplemental data 1. Excel file for the 1779 probes/genes subjected to the clustering analysis. The cluster designation and time dependent change in expression level for each gene are shown. (XLS 5.99 MB)

Footnotes

Received 05 December 2008; received after revision 18 March 2009; accepted 27 March 2009

Contributor Information

G.-J. Jhon, FAX: 82-2-3277-3760, Email: gjjhon@ewha.ac.kr

J. Kim, FAX: 82-2-3277-3760, Email: jkim1964@ewha.ac.kr

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

18_2009_8775_MOESM1_ESM.xls (6MB, xls)

Supplemental data 1. Excel file for the 1779 probes/genes subjected to the clustering analysis. The cluster designation and time dependent change in expression level for each gene are shown. (XLS 5.99 MB)


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