Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold protein PDZK1 and vesicle coat protein Mint3.
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.
Malmberg
Emily K
EK
Department of Medical Biochemistry, Göteborg University, Medicinaregatan 9A, 413 90 Gothenburg, Sweden.
Andersson
Christian X
CX
Gentzsch
Martina
M
Chen
Jey H
JH
Mengos
April
A
Cui
Liying
L
Hansson
Gunnar C
GC
Riordan
John R
JR
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051562:Proto-Oncogene Proteins c-bcr; D020545:Respiratory Mucosa / Q000166:cytology; D022161:Transport Vesicles / Q000378:metabolism*
C117536:APBA3 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008565:Membrane Proteins; C484659:PDZK1 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr