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J Cell Sci ; 117(Pt 23): 5535-41, 2004 Nov 01.
Article in English | MEDLINE | ID: mdl-15494376

ABSTRACT

The breakpoint cluster region protein (Bcr) is a large soluble oligomeric multidomain protein best known because of its involvement in chronic myelogenous leukemia (CML). A chromosomal translocation between its gene and that of the c-abl kinase ('Philadelphia chromosome') plays a major causative role in that malignancy. Thus most attention has been paid to the role of the protein in hemopoietic cells. However, Bcr is also expressed in other cell types including epithelia. Bcr is generally considered to be a cytoplasmic protein but in addition to its kinase and GTPase exchange and activating domains it contains potentially membrane-interacting pleckstrin homology and C2 domains as well as a PDZ-binding C terminus mediating an interaction with a PDZ-domain protein at intercellular junctions of epithelial cells. We have examined the ability of Bcr to interact with other epithelial PDZ proteins and found specific binding to both the apical PDZK1 protein and the Golgi-localized Mint3. The former is important in the organization of several apical functions and the latter in vesicular trafficking in the secretory pathway. Hence these findings extend the interactions and likely signaling impact of Bcr in epithelia from the cytosol to at least these two membrane compartments.


Subject(s)
Carrier Proteins/metabolism , Cell Membrane/metabolism , Epithelial Cells/metabolism , Protein-Tyrosine Kinases/metabolism , Proteins/metabolism , Proto-Oncogene Proteins/metabolism , Transport Vesicles/metabolism , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Animals , Carrier Proteins/chemistry , Carrier Proteins/genetics , Cell Compartmentation/physiology , Cricetinae , Cytosol/metabolism , Golgi Apparatus/metabolism , HT29 Cells , Humans , Membrane Proteins , Molecular Sequence Data , Protein Binding/physiology , Protein Structure, Tertiary/physiology , Protein Transport/physiology , Proto-Oncogene Proteins c-bcr , Respiratory Mucosa/cytology
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