The protein kinase LKB1 negatively regulates bone morphogenetic protein receptor signaling
Raja E, Tzavlaki K, Vuilleumier R, Edlund K, Kahata K, Zieba A, Moren A, Watanabe Y, Voytyuk I, Botling J, Söderberg O, Micke P, Pyrowolakis G, Heldin CH, Moustakas A.
Oncotarget. 2016;7(2):1120-43.
Using cell culture (osteoblast differentiation) and in vivo assays (appendage patterning in Drosophila) we demonstrate that the protein kinase and tumor suppressor LKB1 blocks BMP signalling by channeling type I BMP receptors into ubiquitin/proteosomal-dependent degradation. In addition, our study uncovers a negative correlation of LKB1 loss-of-function and BMP signalling activity in a number of lung cancer patients, highlighting the importance of LKB1-dependent regulation of BMP signalling under both physiological and aberrant conditions.
