Figure 8

Schematic diagram of how integrin-linked kinase (ILK) and glycogen synthase kinase-3β (GSK-3β) might be involved in the acute radiation response with regard to cell survival, cell cycle progression and initiation of G2 phase arrest. Binding of cells to extracellular matrix (ECM) components via β1-integrins stimulates ILK and downstream targets protein kinase Bα/Akt (PKBα/Akt) (phosphorylation at amino-acid residues Ser473 and Thr308) and GSK-3β (phosphorylation at amino-acid residue Ser9). These events suppress apoptosis and promote survival by inhibiting Bad and caspase-9 and cell cycle transition by blocking proteolysis of cyclin D1. Facilitating growth factor binding to growth factor receptors (GFR) activates similar pathways downstream of the central regulator phosphatidylinositol-3 kinase (PI3-K). In bold letters, arrows and circles, we suggest and thereby support the hypothesis of direct ILK phosphorylation of GSK-3β when PI3-K is inhibited and cells are attached to ECM. Irradiation (IR) is able to activate this pathway, which then does not stimulate proliferation but rather blocks cells in the G2 phase possibly allowing damage repair.