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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Gretz, N. Gallagher, A. R. Cedzich, A. Witzgall, R. Somlo, S. |
Description | Author Affiliation: Gallagher AR ( Institute for Anatomy and Cell Biology I, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.); |
Abstract | Despite the recent positional cloning of the PKD1 and PKD2 genes, which are mutated in the great majority of patients with autosomal-dominant polycystic kidney disease (PKD), the pathogenic mechanism for cyst formation is still unclear. The finding, that the PKD1 and PKD2 proteins interact with each other through their COOH termini, suggests that both proteins are part of the same protein complex or signal transduction pathway. Using a yeast two-hybrid screen with the PKD2 protein, we isolated the PKD2-interacting protein Hax-1. The specificity of the interaction was demonstrated by the fact that PKD2L, a protein closely related to PKD2, failed to interact with Hax-1. Immunofluorescence experiments showed that in most cells PKD2 and Hax-1 colocalized in the cell body, but in some cells PKD2 and Hax-1 also were sorted into cellular processes and lamellipodia. Furthermore we demonstrated an association between Hax-1 and the F-actin-binding protein cortactin, which suggests a link between PKD2 and the actin cytoskeleton. We speculate that PKD2 is involved in the formation of cell-matrix contacts, which are dysfunctional without a wild-type PKD2 protein, thus leading to cystic enlargement of tubular structures in the kidney, liver, and pancreas. |
ISSN | 00278424 |
e-ISSN | 10916490 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Issue Number | 8 |
Volume Number | 97 |
Language | English |
Publisher | National Academy of Sciences |
Publisher Date | 2000-05-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Actins Metabolism Cytoskeleton Membrane Proteins Proteins Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Cell Line Cortactin Immunohistochemistry Chemistry Microfilament Proteins Molecular Sequence Data Polycystic Kidney Diseases Precipitin Tests Protein Binding Recombinant Proteins Sequence Homology, Amino Acid TRPP Cation Channels Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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