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In GIST cells, mutant KIT is retained in the Golgi/TGN during biosynthesis. It activates the PLCγ2-PKD2-PI4KIIIβ pathway to generate PI4P. Subsequently, PI4P recruits AP1 and GGA1 adaptors, and the complex retains KIT in the Golgi/TGN. Inhibition of this pathway by a PKD inhibitor, PKD2 knockdown, or tyrosine kinase inhibitors (TKIs) dissociates the KIT mutant from the Golgi/TGN to the PM. TKI blocks tyrosine kinase activity-dependent endocytosis, resulting in KIT retention on the PM. KIT activity is retained in the presence of PKD inhibitor, and the mutant undergoes EIPA-sensitive endocytosis and is degraded in lysosomes. See also Figures S6 and S7.

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