Abstract
Understanding how cells spatially organize signaling events is important in normal biology and pathological conditions such as cancer. Here, we uncover a membraneless, protein granule-based subcellular structure that can organize receptor tyrosine kinase (RTK)-mediated RAS/MAPK pathway signaling, which is thought to occur exclusively from lipid-membrane compartments in mammalian cells. De-novo assembly of cytoplasmic protein granules by certain RTKs, including oncogenic gene fusions involving ALK and RET, is dependent on multimerization domains in the RTK fusion partners. Protein granule formation is both necessary and sufficient to locally concentrate the RAS activating complex GRB2/SOS1 to initiate MAPK pathway signaling. Our findings reveal membraneless, higher-order protein assembly as a principle by which cells can organize kinase-mediated proliferative signals.
One Sentence Summary Kinase/RAS signaling via protein granules
