TY - JOUR
T1 - The mitogen-activated protein kinase signaling pathways: role in megakaryocyte differentiation
AU - Severin, Sonia
AU - Ghevaert, Cedric
AU - Mazharian, Alexandra
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Megakaryopoiesis is a process by which bone marrow progenitor cells develop into mature megakaryocytes (MKs), which in turn produce platelets required for normal hemostasis. The mitogen-activated protein kinases (MAPKs) family comprises four main groups of proteins: extracellular signal-related kinases (ERKs) (ERK1/2 or p44/p42), ERK5, p38MAPKs (alpha, beta, gamma, delta) and c-Jun amino-terminal kinases (JNKs) (JNK 1, 2, 3). These intracellular signaling pathways play a pivotal role in many essential cellular processes including proliferation and differentiation. The purpose of this review is to summarize our current knowledge on the role of MAPKs in MKs, specifically regarding differentiation in immortalized cell lines and primary MKs. A critical role of the MEK (MAPK kinase)-ERK1/2 pathway in MK development has been demonstrated although the details remain controversial. There is at present no functional evidence for a role of p38MAPKs whereas the role of JNKs and ERK5 in MK development is not known. Characterization of these molecular event cascades remains crucial for the understanding of the megakaryopoiesis process.
AB - Megakaryopoiesis is a process by which bone marrow progenitor cells develop into mature megakaryocytes (MKs), which in turn produce platelets required for normal hemostasis. The mitogen-activated protein kinases (MAPKs) family comprises four main groups of proteins: extracellular signal-related kinases (ERKs) (ERK1/2 or p44/p42), ERK5, p38MAPKs (alpha, beta, gamma, delta) and c-Jun amino-terminal kinases (JNKs) (JNK 1, 2, 3). These intracellular signaling pathways play a pivotal role in many essential cellular processes including proliferation and differentiation. The purpose of this review is to summarize our current knowledge on the role of MAPKs in MKs, specifically regarding differentiation in immortalized cell lines and primary MKs. A critical role of the MEK (MAPK kinase)-ERK1/2 pathway in MK development has been demonstrated although the details remain controversial. There is at present no functional evidence for a role of p38MAPKs whereas the role of JNKs and ERK5 in MK development is not known. Characterization of these molecular event cascades remains crucial for the understanding of the megakaryopoiesis process.
KW - 2
KW - ERK1
KW - MAPKs
KW - p38MAPKs
KW - megakaryocyte differentiation
KW - JNKs
U2 - 10.1111/j.1538-7836.2009.03658.x
DO - 10.1111/j.1538-7836.2009.03658.x
M3 - Review article
C2 - 19874462
SN - 1538-7836
VL - 8
SP - 17
EP - 26
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 1
ER -