Interaction of bcl-2 with Paxillin through Its BH4 Domain Is Important during Ureteric Bud Branching

bcl-2 protects cells from apoptosis initiated by a variety of stimuli including loss of cell adhesion. Mice deficient in bcl-2 (bcl-2-/-) develop renal hypoplastic/cystic dysplasia, a condition that leads to significant morbidity and mortality in children. The precise mechanism of action of bcl-2 ha...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-03, Vol.279 (12), p.11368-11374
Main Author: Sorenson, Christine M.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
Cell Line
Cytoskeletal Proteins - chemistry
Cytoskeletal Proteins - metabolism
DNA Primers
Humans
Molecular Sequence Data
Paxillin
Phosphoproteins - chemistry
Phosphoproteins - metabolism
Protein Binding
Proto-Oncogene Proteins c-bcl-2 - chemistry
Proto-Oncogene Proteins c-bcl-2 - metabolism
Ureter - embryology
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Summary:bcl-2 protects cells from apoptosis initiated by a variety of stimuli including loss of cell adhesion. Mice deficient in bcl-2 (bcl-2-/-) develop renal hypoplastic/cystic dysplasia, a condition that leads to significant morbidity and mortality in children. The precise mechanism of action of bcl-2 has not been elucidated. bcl-2 may merely facilitate survival of precursor cells and/or may play a more “active” role during morphogenesis by interacting with other proteins such as paxillin. Recent work in this laboratory demonstrated that bcl-2 directly associates with paxillin. The data presented here demonstrate that the bcl-2 homology 4 (BH4) domain, specifically amino acids 17–31, is necessary for the bcl-2 interaction with paxillin. Paxillin also associated with the BH4 domains of more closely related bcl-2 family members, bcl-xL and bcl-w, compared with that from the non-mammalian homologue ced9. Tyrosines 21 and 28 in the bcl-2 BH4 domain were essential for interaction with paxillin. In embryonic kidney organ culture, incubation with the bcl-2 BH4 domain resulted in inhibition of ureteric bud branching. Therefore, these data suggest that the interaction of bcl-2 with paxillin plays an important role during nephrogenesis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M310079200