Linked Life Data

15872073

Source:http://linkedlifedata.com/resource/pubmed/id/15872073

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-6-29
pubmed:abstractText
Alterations in the cellular architecture, adhesion, and/or loss of glomerular podocytes are causal factors in the development of proteinuria and the progression to end-stage renal failure. With the use of an inducible podocyte differentiation system, it was found that the cellular levels of PINCH-1, integrin linked kinase (ILK), and alpha-parvin, cytoplasmic components of cell-extracellular matrix adhesions, were significantly increased during podocyte differentiation. Concomitantly, an increased amount of the PINCH-1-ILK-alpha-parvin complex was detected in the differentiated, foot process-containing podocytes. Overexpression of the PINCH-1-binding ankyrin repeat domain of ILK but not that of a PINCH-1-binding defective mutant form of the ankyrin domain effectively inhibited the formation of the PINCH-1-ILK-alpha-parvin complex. Disruption of the PINCH-1-ILK-alpha-parvin complex significantly reduced the podocyte-matrix adhesion and foot process formation. Furthermore, a marked increase of apoptosis in the podocytes in which the assembly of the PINCH-1-ILK-alpha-parvin complex was compromised was detected. Inhibition of ILK with a small compound inhibitor also altered podocyte cytoskeleton and increased apoptosis. Finally, it is shown that alpha-parvin is phosphorylated in podocytes. Mutations at the alpha-parvin N-terminal proline-directed serine phosphorylation sites reduced its complex formation with ILK and resulted in defects in podocyte adhesion, architecture, and survival. These results provide important evidence for a crucial role of the PINCH-1-ILK-alpha-parvin complex in the control of podocyte adhesion, morphology, and survival.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1966-76
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15872073-Actinin, pubmed-meshheading:15872073-Adaptor Proteins, Signal Transducing, pubmed-meshheading:15872073-Animals, pubmed-meshheading:15872073-Apoptosis, pubmed-meshheading:15872073-Cell Adhesion, pubmed-meshheading:15872073-Cell Differentiation, pubmed-meshheading:15872073-Cell Survival, pubmed-meshheading:15872073-Cells, Cultured, pubmed-meshheading:15872073-DNA-Binding Proteins, pubmed-meshheading:15872073-Epithelial Cells, pubmed-meshheading:15872073-Extracellular Matrix, pubmed-meshheading:15872073-Kidney Glomerulus, pubmed-meshheading:15872073-LIM Domain Proteins, pubmed-meshheading:15872073-Membrane Proteins, pubmed-meshheading:15872073-Mice, pubmed-meshheading:15872073-Microfilament Proteins, pubmed-meshheading:15872073-Phosphorylation, pubmed-meshheading:15872073-Protein-Serine-Threonine Kinases
pubmed:year
2005
pubmed:articleTitle
Formation and phosphorylation of the PINCH-1-integrin linked kinase-alpha-parvin complex are important for regulation of renal glomerular podocyte adhesion, architecture, and survival.
pubmed:affiliation
707B Scaife Hall, Department of Pathology, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural