Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation
Open Access
- 1 April 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 17 (7), 926-940
- https://doi.org/10.1101/gad.255603
Abstract
Integrin-mediated cell–matrix interactions are essential for development, tissue homeostasis, and repair. Upon ligand binding, integrins are recruited into focal adhesions (FAs). Integrin-linked kinase (ILK) is an FA component that interacts with the cytoplasmic domains of integrins, recruits adaptor proteins that link integrins to the actin cytoskeleton, and phosphorylates the serine/threonine kinases PKB/Akt and GSK-3β. Here we show that mice lacking ILK expression die at the peri-implantation stage because they fail to polarize their epiblast and to cavitate. The impaired epiblast polarization is associated with abnormal F-actin accumulation at sites of integrin attachments to the basement membrane (BM) zone. Likewise, ILK-deficient fibroblasts showed abnormal F-actin aggregates associated with impaired cell spreading and delayed formation of stress fibers and FAs. Finally, ILK-deficient fibroblasts have diminished proliferation rates. However, insulin or PDGF treatment did not impair phosphorylation of PKB/Akt and GSK-3β, indicating that the proliferation defect is not due to absent or reduced ILK-mediated phosphorylation of these substrates in vivo. Furthermore, expression of a mutant ILK lacking kinase activity and/or paxillin binding in ILK-deficient fibroblasts can rescue cell spreading, F-actin organization, FA formation, and proliferation. Altogether these data show that mammalian ILK modulates actin rearrangements at integrin-adhesion sites.Keywords
This publication has 43 references indexed in Scilit:
- PINCH2 is a new five LIM domain protein, homologous to PINCHand localized to focal adhesions☆Experimental Cell Research, 2003
- Interaction of alphaPIX (ARHGEF6) with beta-parvin (PARVB) suggests an involvement of alphaPIX in integrin-mediated signalingHuman Molecular Genetics, 2003
- Characterization of PINCH-2, a New Focal Adhesion Protein That Regulates the PINCH-1-ILK Interaction, Cell Spreading, and MigrationPublished by Elsevier BV ,2002
- IntegrinsCell, 2002
- Identification of a Plasma Membrane Raft-Associated PKB Ser473 Kinase Activity that Is Distinct from ILK and PDK1Current Biology, 2002
- Molecular Dissection of Actopaxin-Integrin-linked Kinase-Paxillin Interactions and Their Role in Subcellular LocalizationPublished by Elsevier BV ,2002
- A Novel Integrin-Linked Kinase–Binding Protein, Affixin, Is Involved in the Early Stage of Cell–Substrate InteractionThe Journal of cell biology, 2001
- Integrin-linked Kinase (ILK) Binding to Paxillin LD1 Motif Regulates ILK Localization to Focal AdhesionsPublished by Elsevier BV ,2001
- Synergism among Lysophosphatidic Acid, β1A Integrins, and Epidermal Growth Factor or Platelet-derived Growth Factor in Mediation of Cell MigrationPublished by Elsevier BV ,1999
- Regulation of cell adhesion and anchorage-dependent growth by a new β1-integrin-linked protein kinaseNature, 1996