MAPK signaling pathways in the regulation of hematopoiesis.
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.
Geest
Christian R
CR
Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Coffer
Paul J
PJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D038042:Myelopoiesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases