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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0209097

Received for publication February 22, 2009.
Revised March 29, 2009.
Accepted for publication April 1, 2009.

Review

MAPK signaling pathways in the regulation of hematopoiesis

Christian R. Geest * and Paul J. Coffer *{dagger}@

*Molecular Immunology Laboratory, Department of Immunology, and{dagger}Department of Pediatric Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

@ To whom correspondence should be addressed. E-mail: p.j.coffer{at}umcutrecht.nl.


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Abstract

The MAPKs are a family of serine/threonine kinases that play an essential role in connecting cell-surface receptors to changes in transcriptional programs. MAPKs are part of a three-component kinase module consisting of a MAPK, an upstream MEK, and a MEKK that couples the signals from cell-surface receptors to trigger downstream pathways. Three major groups of MAPKs have been characterized in mammals, including ERKs, JNKs, and p38MAPKs. Over the last decade, extensive work has established that these proteins play critical roles in the regulation of a wide variety of cellular processes including cell growth, migration, proliferation, differentiation, and survival. It has been demonstrated that ERK, JNK, and p38MAPK activity can be regulated in response to a plethora of hematopoietic cytokines and growth factors that play critical roles in hematopoiesis. In this review, we summarize the current understanding of MAPK function in the regulation of hematopoiesis in general and myelopoiesis in particular. In addition, the consequences of aberrant MAPK activation in the pathogenesis of various myeloid malignancies will be discussed.

Key Words: CD34+ • signal transduction • transcription • ERK • p38 • JNK




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