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PMID: 12671688 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Integrin-linked kinase regulates chondrocyte shape and proliferation.

EMBO reports ·Vol. 4 ·No. 4 ·2003-04-00 ·Pages 432-8

Grashoff C, Aszódi A, Sakai T, Hunziker EB, Fässler R

Abstract

The interaction of chondrocytes with the extracellular-matrix environment is mediated mainly by integrins. Ligated integrins are recruited to focal adhesions (FAs) together with scaffolding proteins and kinases, such as integrin-linked kinase (Ilk). Ilk binds the cytoplasmic domain of beta1-, beta2- and beta3-integrins and recruits adaptors and kinases, and is thought to stimulate downstream signalling events through phosphorylation of protein kinase B/Akt (Pkb/Akt) and glycogen synthase kinase 3-beta (GSK3-beta). Here, we show that mice with a chondrocyte-specific disruption of the gene encoding Ilk develop chondrodysplasia, and die at birth due to respiratory distress. The chondrodysplasia was characterized by abnormal chondrocyte shape and decreased chondrocyte proliferation. In addition, Ilk-deficient chondrocytes showed adhesion defects, failed to spread and formed fewer FAs and actin stress fibres. Surprisingly, phosphorylation of Pkb/Akt and GSK3-beta is unaffected in Ilk-deficient chondrocytes. These findings suggest that Ilk regulates actin reorganization in chondrocytes and modulates chondrocyte growth independently of phosphorylation of Pkb/Akt and GSK3-beta.

MeSH Terms
Animals Cell Division/physiology Cell Size/physiology Cells, Cultured Chondrocytes/drug effects,physiology Glycogen Synthase Kinase 3/metabolism Glycogen Synthase Kinase 3 beta In Situ Hybridization Mice Mice, Knockout Mice, Transgenic Phosphorylation Protein Serine-Threonine Kinases/deficiency,genetics,metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-akt
Chemicals
Proto-Oncogene Proteins integrin-linked kinase Glycogen Synthase Kinase 3 beta Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Glycogen Synthase Kinase 3
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Grashoff Carsten
Department of Molecular Medicine, Max Planck Institute for Biochemistry, Martinsried, Germany.
Aszódi Attila
Sakai Takao
Hunziker Ernst B
Fässler Reinhard
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.embor801
Published
2003-04-00
Pages
432-8
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1319157
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.embor.embor801 PMC Full Text View journal details
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