Genome-wide screen of gamma-secretase-mediated intramembrane cleavage of receptor tyrosine kinases.

ABSTRACT: Receptor tyrosine kinases (RTKs) have been demonstrated to signal via regulated intramembrane proteolysis, in which ectodomain shedding and subsequent intramembrane cleavage by gamma-secretase leads to release of a soluble intracellular receptor fragment with functional activity. For most RTKs, however, it is unknown whether they can exploit this new signaling mechanism. Here we used a system-wide screen to address the frequency of susceptibility to gamma-secretase cleavage among human RTKs. The screen covering 45 of the 55 human RTKs identified 12 new as well as all nine previously published gamma-secretase substrates. We biochemically validated the screen by demonstrating that the release of a soluble intracellular fragment from endogenous AXL was dependent on the sheddase disintegrin an

SUBMITTER: Merilahti JAM 

PROVIDER: S-EPMC5662267 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature