Nephrocystin interacts with Pyk2, p130Cas, and tensin and triggers phosphorylation of Pyk2
AUTOR(ES)
Benzing, Thomas
FONTE
National Academy of Sciences
RESUMO
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 p130Cas 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 p130Cas, 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=55530Documentos Relacionados
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