Journal
CELLULAR SIGNALLING
Volume 19, Issue 4, Pages 740-747Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2006.09.007
Keywords
NPM-ALK; kinase; NFAT; AP-1; ALCL
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C199] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C199] Funding Source: researchfish
Ask authors/readers for more resources
Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) expression is associated with the lymphoid malignancy anaplastic large cell lymphoma (ALCL) and results from a t(2;5) chromosomal translocation. We show that NPM-ALK induces Ras activation and phosphorylation of the ERK MAP Kinase consistent with activation of the Ras-MAP Kinase pathway. Furthermore, we demonstrate that activation of Ras is necessary for inducing transcription via NFAT/AP-1 composite transcriptional binding sites. This activity is dependent on NPM-ALK forming complexes with proteins that bind to autophosphorylated tyrosine residues at positions 156, 567 and 664, associated with binding to IRS-1, She and PLC gamma, respectively. Specifically, NPM-ALK activates transcription from the TRE promoter element, an AP-1 binding region, an activity dependent on both Ras and Shc activity. Our results show that NPM-ALK mimics activated T-cell receptor signalling by inducing pathways associated with the activation of NFAT/AP-1 transcription factors that bind to promoter elements found in a broad array of cytokine genes. (c) 2006 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available