Interaction of bcl-2 with Paxillin through its BH4 domain is important during ureteric bud branching

J Biol Chem. 2004 Mar 19;279(12):11368-74. doi: 10.1074/jbc.M310079200. Epub 2003 Dec 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Cytoskeletal Proteins
  • DNA Primers
  • PXN protein, human
  • Paxillin
  • Phosphoproteins
  • Proto-Oncogene Proteins c-bcl-2