Integrins are adhesion receptors consisting of two different subunits, termed a and ß. They play crucial roles in cell
adhesion and migration and in concert with other cellular signal transducing machineries control growth, survival
and differentiation of cells. Integrins have the ability to serve as bidirectional signalling receptors. Ligand binding
leads to cell adhesion and transduction of signals into cells, while intracellular signals can induce conformational
changes of integrin molecules which modulate their affinity.
The kinase ILK and the two adapter proteins PINCH 1 and PINCH2 are proteins that link integrin ß1 to the
intracellular signalling cascade. Loss of ILK and PINCH1 mimics some but not all of the aspects of integrin ß1(-/-
) phenotype. The reason for this discrepancy is not clear but the newly identified PINCH2 may rescue PINCH1
deficiency in part. This research project aims at resolving these discrepancies by defining the role of individual
domains of ILK, PINCH1 and PINCH2. For this purpose a combination of in vivo (knock-out and knock-in
strategy in mice) and in vitro approaches (with cell lines derived from single and double knockout mice) will be
used.