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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
A050053000101.pdf
[fulltext] 524 KB
Title
The Role of MEK Kinase 1 in Bcr-Abl-Induced Self-Renewal Activity of Embryonic Stem Cells
Creators Nakamura Yukinori
Creators Yujiri Toshiaki
Creators Tanizawa Yukio
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.
Subjects
医学 ( Other)
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