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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-12-19
pubmed:abstractText
The integrin-linked kinase (ILK) serves as an adapter protein to link the cytoplasmic domains of integrins with cytoskeletal components. Organization of the actin cytoskeleton is strongly influenced by the small GTPase RhoA, which also regulates gene expression. To investigate the impact of ILK deficiency on RhoA-mediated signaling we used ILK-deficient fibroblasts. The cytoskeleton of ILK (-/-) cells was characterized by less organized F-actin fibers, compared to wild type mouse fibroblasts. Stimulation of the cells with lysophosphatidic acid (LPA) or the microtubule disrupting agent colchicine increased polymerization of F-actin stress fibers in ILK (+/+) cells, whereas ILK (-/-) cells showed a network of short thin cortical actin fibers, cell rounding and finally detachment from the surface of the culture plates. The structural changes were primarily attributable to the activation of RhoA in both cell types. ILK deficiency also affected gene expression. The basal levels of several proteins related to fibroblast differentiation, such as connective tissue growth factor (CTGF), thrombospondin 1 and alpha smooth muscle actin, were reduced in ILK (-/-) cells. However, induction of CTGF expression by LPA or colchicine was comparable in ILK (+/+) and ILK (-/-) cells. Furthermore, stimulation of CTGF or thrombospondin by TGFbeta was not reduced by ILK deficiency. Inhibition of the RhoA-associated kinase or overexpression of dominant negative RhoA reduced the stimulated CTGF expression indicative of a role for RhoA signaling in CTGF expression. Taken together, ILK is involved in RhoA-dependent reorganization of the actin cytoskeleton, whereas activation of RhoA and RhoA-mediated gene expression is independent of ILK.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0898-6568
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
433-40
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Differential involvement of the integrin-linked kinase (ILK) in RhoA-dependent rearrangement of F-actin fibers and induction of connective tissue growth factor (CTGF).
pubmed:affiliation
Medizinische Klinik IV, Universität Erlangen-Nürnberg, Loschgestrasse 8, D-91054 Erlangen, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't