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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-12
pubmed:abstractText
We analysed the subcellular distribution of p210(BCR-ABL) protein using a junction-specific anti-BCR-ABL monoclonal antibody and confocal laser scanning microscopy (CLSM). Our studies have shown that p210(BCR-ABL) is arranged in discrete foci in the cytoplasm of cell lines and primary CD34(+) cells but not mononuclear cells suggesting the foci may be a feature of immature chronic myeloid leukaemia cells. We have devised a strategy to score the foci and found the mean number of foci varies between the cell types. The number of foci per cell is directly related to the level of p210(BCR-ABL) expression. CLSM was also used to analyse the distribution and colocalization of CT10 regulator-like (CRKL) p210(BCR-ABL). CRKL-p210(BCR-ABL) foci were completely or partially associated, touching or separate in different regions of the same cell. We also analysed the distribution of phosphorylated CRKL (pCRKL) with p210(BCR-ABL) and unexpectedly found only a small proportion of pCRKL in complex with p210(BCR-ABL). The foci distribution and high levels of uncomplexed p210(BCR-ABL), pCRKL and CRKL protein suggested the possibility of a dynamic equilibrium. Imatinib promoted nuclear transport of p210(BCR-ABL)-positive foci. It also disrupted complex formation between p210(BCR-ABL) and casitas B-cell lymphoma and CRKL but not between p210(BCR-ABL) and GRB2. Our observations of the CRKL and p210(BCR-ABL) complex may be important for understanding the function of CRKL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5551
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
559-71
pubmed:meshHeading
pubmed-meshheading:18059481-Active Transport, Cell Nucleus, pubmed-meshheading:18059481-Adaptor Proteins, Signal Transducing, pubmed-meshheading:18059481-Antibody Specificity, pubmed-meshheading:18059481-Antineoplastic Agents, pubmed-meshheading:18059481-Cell Aging, pubmed-meshheading:18059481-Cell Line, Tumor, pubmed-meshheading:18059481-Fusion Proteins, bcr-abl, pubmed-meshheading:18059481-Humans, pubmed-meshheading:18059481-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:18059481-Leukocytes, Mononuclear, pubmed-meshheading:18059481-Microscopy, Confocal, pubmed-meshheading:18059481-Neoplastic Stem Cells, pubmed-meshheading:18059481-Nuclear Proteins, pubmed-meshheading:18059481-Phosphorylation, pubmed-meshheading:18059481-Piperazines, pubmed-meshheading:18059481-Protein Interaction Mapping, pubmed-meshheading:18059481-Protein Kinase Inhibitors, pubmed-meshheading:18059481-Protein Processing, Post-Translational, pubmed-meshheading:18059481-Pyrimidines, pubmed-meshheading:18059481-Subcellular Fractions
pubmed:year
2008
pubmed:articleTitle
Subcellular distribution of p210(BCR-ABL) in CML cell lines and primary CD34+ CML cells.
pubmed:affiliation
Department of Haematology, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't