Document Detail


Novel role of pleckstrin homology domain of the Bcr-Abl protein: analysis of protein-protein and protein-lipid interactions.
MedLine Citation:
PMID:  19944685     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Bcr-Abl protein is a marker for malignant transformation in chronic myeloid leukemia and in acute lymphoblastic leukemia. There are three Bcr-Abl chimeras known so far, p190, p210 and p230. The only structural difference between the three Bcr-Abl proteins is the presence of DH and PH domains from the Bcr gene in p210 and p230. The Bcr-Abl DH domain is functioning as a guanine nucleotide exchange factor for Rho family of small GTPases. The PH domain confers binding to phosphoinositides but some PH domains have also been found to bind specific target proteins. Here we show that the PH domain from Bcr-Abl binds a number of proteins involved in vital cellular processes. These proteins include PLCvarepsilon, Zizimin1, tubulin and SMC1. The revelation of the role of the Bcr-Abl PH domain in leukemogenesis is likely to provide clues to the molecular mechanisms underlying the phenotypes of Bcr-Abl positive leukemia and could therefore provide tools for the identification of targets for the development of therapeutic treatments.
Authors:
Daria Miroshnychenko; Anna Dubrovska; Stanislav Maliuta; Gennady Telegeev; Pontus Aspenstr?m
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-26
Journal Detail:
Title:  Experimental cell research     Volume:  316     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-03-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  530-42     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
Affiliation:
Institute of Molecular Biology and Genetics NAS of Ukraine, Zabolotnogo str, 150 Kyiv 03143, Ukraine.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers
COS Cells
Cell Line
Cercopithecus aethiops
Electrophoresis, Polyacrylamide Gel
Genes, abl / genetics,  physiology*
Humans
Intracellular Signaling Peptides and Proteins* / genetics,  physiology
K562 Cells
Microscopy, Fluorescence
Phosphatidylinositols / metabolism*
Protein Binding
Proteomics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Intracellular Signaling Peptides and Proteins; 0/PHIP protein, human; 0/Phosphatidylinositols

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