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 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.
Sorenson
Christine M
CM
Department of Pediatrics, University of Wisconsin, Madison, Wisconsin 53792, USA. cmsorenson@wisc.edu
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D008969:Molecular Sequence Data; D051419:Paxillin; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D014513:Ureter / Q000196:embryology*
D003598:Cytoskeletal Proteins; D017931:DNA Primers; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2