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Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9784-9. Epub 2001 Aug 7.

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

Author information

  • 1Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany; and Children's Hospital, and Molecular Medicine, University of Freiburg, 79106 Freiburg, Germany.

Abstract

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.

PMID:
11493697
[PubMed - indexed for MEDLINE]
PMCID:
PMC55530
Free PMC Article

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