Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells.

Donaldson JC, Dempsey PJ, Reddy S, Bouton AH, Coffey RJ, Hanks SK
Exp Cell Res. 2000 256 (1): 168-78

PMID: 10739664 · DOI:10.1006/excr.2000.4822

Crk-associated substrate (p130(Cas), Cas) is a docking protein first recognized as having elevated phosphotyrosine content in mammalian cells transformed by v-Src and v-Crk oncoproteins. Subsequent studies have implicated Cas in the control of normal cell behavior through its roles in integrin-mediated signal transduction and organization of the actin cytoskeleton at sites of cell adhesion. In this study, we sought to gain new insight into normal Cas function by identifying previously unrecognized interacting proteins. A yeast two-hybrid screen using the C-terminal region of Cas as a bait identified the Src homology 3 (SH3) domain of the mouse "nephrocystin" protein-orthologous to a human protein whose loss of function leads to the cystic kidney disease familial juvenile nephronophthisis. The putative full-length mouse and partial canine nephrocystin sequences were deduced from cDNA clones. Additional studies using epitope-tagged mouse nephrocystin indicated that nephrocystin and Cas can interact in mammalian cells and revealed that both proteins prominently localize at or near sites of cell-cell contact in polarized Madin-Darby canine kidney epithelial cells. Our findings provide novel insight into the normal cellular activities regulated by both Cas and nephrocystin, and raise the possibility that these proteins have a related function in polarized epithelial cells.

Copyright 2000 Academic Press.

MeSH Terms (29)

Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Cell Line Cell Polarity Cell Transformation, Neoplastic Crk-Associated Substrate Protein Dogs Epithelial Cells Genes, src Humans Intercellular Junctions Kidney Membrane Proteins Mice Molecular Sequence Data Oncogene Protein v-crk Phosphoproteins Proteins Recombinant Proteins Retinoblastoma-Like Protein p130 Retinoblastoma Protein Retroviridae Proteins, Oncogenic Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Sequence Homology, Amino Acid src Homology Domains Transcription, Genetic Transfection

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