Integrin-Linked Kinase Regulates Endothelial Cell Survival and Vascular Development
Open Access
- 1 September 2004
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 24 (18), 8134-8144
- https://doi.org/10.1128/mcb.24.18.8134-8144.2004
Abstract
Integrin-linked kinase (ILK) is a phosphoinositide 3-kinase-dependent serine/threonine kinase that interacts with β integrins. Here we show that endothelial cell (EC)-specific deletion of ILK in mice confers placental insufficiency with decreased labyrinthine vascularization, yielding no viable offspring. Deletion of ILK in zebra fish using antisense morpholino oligonucleotides results in marked patterning abnormalities of the vasculature and is similarly lethal. To dissect potential mechanisms responsible for these phenotypes, we performed ex vivo deletion of ILK from purified EC of adult mice. We observed downregulation of the active-conformation of β1 integrins with a striking increase in EC apoptosis associated with activation of caspase 9. There was also reduced phosphorylation of the ILK kinase substrate, Akt. However, phenotypic rescue of ILK-deficient EC by wild-type ILK, but not by a constitutively active mutant of Akt, suggests regulation of EC survival by ILK in an Akt-independent manner. Thus, endothelial ILK plays a critical role in vascular development through integrin-matrix interactions and EC survival. These data have important implications for both physiological and pathological angiogenesis.Keywords
This publication has 42 references indexed in Scilit:
- Regulation of tumor angiogenesis by integrin-linked kinase (ILK)Cancer Cell, 2004
- Integrin-linked kinase is required for laminin-2–induced oligodendrocyte cell spreading and CNS myelinationThe Journal of cell biology, 2003
- Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytesThe Journal of cell biology, 2003
- Integrins: Bidirectional, Allosteric Signaling MachinesCell, 2002
- A Critical Role of the PINCH-Integrin-linked Kinase Interaction in the Regulation of Cell Shape Change and MigrationOnline Journal of Public Health Informatics, 2002
- Cell–substrate interactions and signaling through ILKCurrent Opinion in Cell Biology, 2000
- Patterns and Emerging Mechanisms of the Angiogenic Switch during TumorigenesisCell, 1996
- Regulation of cell adhesion and anchorage-dependent growth by a new β1-integrin-linked protein kinaseNature, 1996
- Monoclonal Antibody 9EG7 Defines a Novel β1 Integrin Epitope Induced by Soluble Ligand and Manganese, but Inhibited by CalciumOnline Journal of Public Health Informatics, 1995
- Requirement of Vascular Integrin α v β 3 for AngiogenesisScience, 1994