Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion
作者： Christine Gundry , Sergi Marco , Elena Rainero , Bryan Miller , Emmanuel Dornier
DOI: 10.1038/NCOMMS14646
关键词:
摘要: The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis vivo unclear. Here we identify an RTK of the Eph family, EphA2, be a cargo RCP-regulated endocytic pathway which controls cell:cell repulsion vivo. Phosphorylation at Ser435 Lemur kinase-3 (LMTK3) EphA2 Ser897 Akt are both necessary Rab14-dependent (and Rab11-independent) trafficking generates events that drive tumour cells apart. Genetic disruption or opposes autochthonous mouse model pancreatic adenocarcinoma-whereas conditional knockout another cargo, α5 integrin, does not suppress cancer metastasis-indicating role for RCP-dependent dissemination
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