Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2.

Juvenile nephronophthisis type 1 is caused by mutations of NPHP1, the gene encoding for nephrocystin. The function of nephrocystin is presently unknown, but the presence of a Src homology 3 domain and its recently described interaction with p130(Cas) suggest that nephrocystin is part of the focal adhesion signaling complex. We ...
generated a nephrocystin-specific antiserum and analyzed the interaction of native nephrocystin with endogenous proteins. Immunoprecipitation of nephrocystin revealed that nephrocystin forms protein complexes with p130(Cas), proline-rich tyrosine kinase 2 (Pyk2), and tensin, indicating that these proteins participate in a common signaling pathway. Expression of nephrocystin resulted in phosphorylation of Pyk2 on tyrosine 402 as well as activation of downstream mitogen-activated protein kinases, such as ERK1 and ERK2. Our findings suggest that nephrocystin helps to recruit Pyk2 to cell matrix adhesions, thereby initiating phosphorylation of Pyk2 and Pyk2-dependent signaling. A lack of functional nephrocystin may compromise Pyk2 signaling in a subset of renal epithelial cells.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Blotting, Western, Cells, Cultured, Crk-Associated Substrate Protein, Epithelial Cells, Focal Adhesion Kinase 2, Humans, Kidney Tubules, Collecting, MAP Kinase Signaling System, Macromolecular Substances, Membrane Proteins, Mice, Microfilament Proteins, Phosphoproteins, Phosphorylation, Phosphotyrosine, Protein Processing, Post-Translational, Protein-Tyrosine Kinases, Proteins, Recombinant Fusion Proteins, Retinoblastoma-Like Protein p130, src Homology Domains
Proc. Natl. Acad. Sci. U.S.A.
Date: Aug. 14, 2001
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