Nakamura Yukinori
Affiliate Master
Yamaguchi University
The Role of MEK Kinase 1 in Bcr-Abl-Induced Self-Renewal Activity of Embryonic Stem Cells
The bulletin of the Yamaguchi Medical School Volume 53 Issue 1-2
Page 1-4
published_at 2006
Title
The Role of MEK Kinase 1 in Bcr-Abl-Induced Self-Renewal Activity of Embryonic Stem Cells
Source Identifiers
Creator Keywords
bcr-abl
mek kinase 1
stat3
self renewal activity
embryonic stem cells
BCR-ABL oncogene, the moecular hallmark of chronic mylogenous leukemia, arises in a promitive hematopoietic stem cell that has the capacity for both differentiation and self-renewal. Its product, Bcr-Abl protein, has been shown to sctivate signal transducers and activators of transcription 3 (STAT3) and to promote self-renewal in embryonic stem (ES)cells, even in the absencs of leukemia in hibitory factor (LIF). MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase involoved in Bcr-Ablsignal transduction. To investigate the role of MEKK1 in bcr-Abl-induced transformation of stem cells, p210 Bcr-Abl was stably transfected into wild type (WTp210)and MEKK1-/-(MEKK1-/-p210) ES cells. Bcr-Abl enhanced MEKK1 expression in ES transfectants, as it does in other Bcr-Abl-transformed cells. In the absence of LIF, WTp210 cells showed constitutive STAT3 activation and formed rounded, compact colonies having strong alkaline phosphatase activity, a characteristic phenotype of undifferentiated ES cells. MEKK1-/-p210 cells, by contrast, showed less STAT3 activity than WTp210 cells and formed large, flattened colonies having weak alkaline phosphatase activity, a phenotype of differentiated ES cells. These results indicate that MEKK1 plays a ker role in Bcr-Abl-induced STAT3 activation and in ES cells's capacity for LIF-independent self-renewal, and may thus be involved in Bcr-Abl-mediated leukemogenesis in stem cells.
Languages
eng
Resource Type
departmental bulletin paper
Publishers
Yamaguchi University School of Medicine
Date Issued
2006
File Version
Version of Record
Access Rights
open access
Relations
[isVersionOf]
[URI]http://ds.cc.yamaguchi-u.ac.jp/~bulletin/index.html
Schools
医学部