Electronic Thesis and Dissertation Repository


Master of Science




Dr. Lina Dagnino


Transforming growth factor-beta 1 (TGF-β1) modulates regeneration after injury through induction of fibroblast proliferation, migration, and differentiation into myofibroblasts. Induction of myofibroblast differentiation by TGF-β1 requires expression of integrin-linked kinase (ILK). I now show that ILK interacts with TGF-β receptor type II (TβRII) in primary dermal fibroblasts. Further, colocalization of ILK and TβRII can be observed at the cell membrane and in intracellular vesicles. The association of TβRII and ILK does not require TGF-β1 stimulation, kinase activity of TGF-β1 receptor type I or TβRII, and it does not involve interactions between ILK and focal adhesion-associated proteins. When this interaction is abolished by targeted inactivation of the Ilk gene, TβR signalling is diminished, as demonstrated by decreased phosphorylated SMAD2 levels in response to TGF-β1 treatment. This can be restored by exogenous expression of human ILK or by inhibition of TβRII degradatory pathway. Thus, ILK is essential for normal TβR signalling.