Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2.
Proc Natl Acad Sci U S A
; 98(17): 9784-9, 2001 Aug 14.
Article
in En
| MEDLINE
| ID: mdl-11493697
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoproteins
/
Protein-Tyrosine Kinases
/
Proteins
/
Protein Processing, Post-Translational
/
Microfilament Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2001
Document type:
Article
Affiliation country:
Germany