Abstract
Mitogen-activated protein (MAP) kinases act as transducers of extracellular signaling via tyrosine kinase-growth factor receptors and G-protein-linked receptors to transcription factors. Constitutive activation of MAP kinase has been observed in a variety of solid tumors including renal cancer and breast cancer. Recently, we have reported that constitutively activated MAP kinase was observed in 50% of human primary acute myeloid leukemia (AML) cells. Ras is one of the components of G-proteins and transduces the signal from cytokine receptors to raf-1 theoretically resulting in the activation of MAP kinase pathway. In the present study, we have examined the correlation of Ras mutations and the activation of MAP kinase pathway in patients with AML. Twenty out of 22 AML cases with activating N-Ras mutations showed no phosphorylated forms of ERK2. ERK2 phosphorylation was tightly correlated with ERK1 phosphorylation and MAP kinase activity detected by in vitro kinase assay. Three samples with N-Ras mutations were stimulated with IL-3, GM-CSF and G-CSF separately but ERK2 activation was induced in none of these samples stimulated with these cytokines. In contrast, ERK2 was constitutively activated in all of four pancreatic carcinoma cases with K-Ras mutation at codon 12. These results suggest that function of the Ras mutations may be different between solid tumors, such as pancreatic carcinoma and colorectal carcinoma, and AML. Mutated Ras does not always stimulate MAP kinase pathway constitutively and may rather inhibit classical MAP kinase cascade in AML blasts from leukemia patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Iida, M., Towatari, M., Nakao, A. et al. Lack of constitutive activation of MAP kinase pathway in human acute myeloid leukemia cells with N-Ras mutation. Leukemia 13, 585–589 (1999). https://doi.org/10.1038/sj.leu.2401369
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2401369
Keywords
This article is cited by
-
Activation of MEK2 is sufficient to induce skin papilloma formation in transgenic zebrafish
Journal of Biomedical Science (2015)
-
Role of Ras/Raf/MEK/ERK signaling in physiological hematopoiesis and leukemia development
Immunologic Research (2011)
-
Kinetics of ERK1/2 activation determine sensitivity of acute myeloid leukaemia cells to the induction of apoptosis by the novel small molecule ingenol 3-angelate (PEP005)
Apoptosis (2010)
-
Ras isoform abundance and signalling in human cancer cell lines
Oncogene (2008)
-
Mapping normal and cancer cell signalling networks: towards single-cell proteomics
Nature Reviews Cancer (2006)