Tsz-Yin Chan, Christina M Egbert, Julia E Maxson, Adam Siddiqui, Logan J Larsen, Kristina Kohler, Eranga Roshan Balasooriya, Katie L Pennington, Tsz-Ming Tsang, Madison Frey, Erik J Soderblom, Huimin Geng, Markus Müschen, Tetyana V Forostyan, Savannah Free, Gaelle Mercenne, Courtney J Banks, Jonard Valdoz, Clifford J Whatcott, Jason M Foulks, David J Bearss, Thomas O'Hare, David C S Huang, Kenneth A Christensen, James Moody, Steven L Warner, Jeffrey W Tyner, Joshua L Andersen
TNK1 is a non-receptor tyrosine kinase with poorly understood biological function and regulation. Here, we identify TNK1 dependencies in primary human cancers. We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity. Conversely, the release of TNK1 from 14-3-3 allows TNK1 to cluster in ubiquitin-rich puncta and become active. Active TNK1 induces growth factor-independent proliferation of lymphoid cells in cell culture and mouse models...
September 9, 2021: Nature Communications