Paxillin's LD4 motif interacts with bcl-2.
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.
Sheibani
Nader
N
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Tang
Yixin
Y
Sorenson
Christine M
CM
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D051419:Paxillin / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017384:Sequence Deletion; D014513:Ureter / Q000166:cytology / Q000187:drug effects