Structural insights into Met receptor activation

Abstract

The receptor tyrosine kinase Met plays a pivotal role in vertebrate development and tissue regeneration, its deregulation contributes to cancer. Met is also targeted during the infection by the facultative intracellular bacterium Listeria monocytogenes. The mechanistic basis for Met activation by its natural ligand hepatocyte growth factor/scatter factor (HGF/SF) is only beginning to be understood at a structural level. Crystal structures of Met in complex with L. monocytogenes InlB suggest that Met dimerization by this bacterial invasion protein is mediated by a dimer contact of the ligand. Here, I review the structural basis of Met activation by InlB and highlight parallels and differences to the physiological Met ligand HGF/SF and its splice variant NK1.