Paxillin's LD4 motif interacts with bcl-2

J Cell Physiol. 2008 Mar;214(3):655-61. doi: 10.1002/jcp.21256.

Abstract

Bcl-2 is the founding member of a family of proteins which influences cell survival in response to a variety of stimuli including those from growth factor receptors and integrins. However, how these activities are coordinated through bcl-2 requires further investigation. bcl-2 interacts with paxillin, potentially linking cell survival and cell adhesive pathways. Paxillin is an adapter protein implicated in growth factor and integrin-mediated signal transduction pathways. Previous work in this laboratory demonstrated that loss of bcl-2 affects cell adhesion and migration characteristics of renal epithelial cells, perhaps through disruption of its interaction with paxillin. Here studies were performed to determine the bcl-2 binding motif in paxillin. The amino-terminal portion of paxillin, specifically its LD4 motif, was found to associate with bcl-2. However, the amino-terminal portion of paxillin with the LD4 domain deleted did not associate with bcl-2. The corresponding LD motif in other paxillin family members, Hic-5 and leupaxin, did not associate with bcl-2. Mutations in paxillin's LD4 motif made to mimic Hic-5 and leupaxin LD4-like motifs (E(268) --> R or S(272) --> H) abolished its association with bcl-2. Incubation of embryonic kidneys with paxillin's LD4 motif disrupted ureteric bud branching and morphogenesis, while incubation with the comparable Hic-5 LD motif did not significantly affect morphogenesis. These data suggest that paxillin's association with bcl-2 plays a unique role during kidney development that other paxillin family members may not be able to fulfill.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Paxillin / chemistry*
  • Paxillin / metabolism*
  • Peptides / chemistry
  • Peptides / pharmacology
  • Phosphoproteins / metabolism
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sequence Deletion
  • Ureter / cytology
  • Ureter / drug effects

Substances

  • Cytoskeletal Proteins
  • Paxillin
  • Peptides
  • Phosphoproteins
  • Proto-Oncogene Proteins c-bcl-2