Fig. 7: The clinically approved tyrosine kinase inhibitors (TKIs) bosutinib and dasatinib impact TGFβ-mediated transcriptional and cellular responses.
From: Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses
a The chemical structures of the clinically approved small-molecule tyrosine kinase inhibitors (TKIs) bosutinib and dasatinib. b In vitro nanomolar IC50 values of bosutinib and dasatinib against the protein kinases Abl, BTK, Src and the three SIK isoforms (adapted from Ozanne et al.45). c Immunoblot analysis of endogenous CRTC3 phosphorylation in wild-type U2OS cells following incubation with DMSO, MRT199665, bosutinib or dasatinib. Cell lysates were subjected to CRTC3 IP and subsequently resolved via SDS-PAGE. Membranes were subjected to immunoblotting with the indicated antibodies. d Immunoblot analysis of U2OS 2G transcriptional reporter cells incubated with SB-505124, bosutinib or dasatinib in the presence of TGFβ1 stimulation. Cell lysates were resolved via SDS-PAGE, and membranes were subjected to immunoblotting with the indicated antibodies. e Immunoblot analysis of wild- type U2OS cells incubated with SB-505124, bosutinib or dasatinib in the presence of TGFβ1 stimulation. Cell lysates were resolved via SDS-PAGE, and membranes were subjected to immunoblotting with the indicated antibodies. f Immunoblot analysis of wild-type NMuMG cells incubated with SB-505124, MRT199665, bosutinib or dasatinib in the presence of TGFβ1 stimulation. Cell lysates were resolved via SDS-PAGE, and membranes were subjected to immunoblotting with the indicated antibodies. g Immunoblot analysis of wild-type NMuMG cells incubated with SB-505124, MRT199665 or bosutinib in the presence of TGFβ1 stimulation. Cell lysates were resolved via SDS-PAGE, and membranes were subjected to immunoblotting with the indicated antibodies.
