Research ArticleCell Biology

The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases

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Science Signaling  18 Sep 2018:
Vol. 11, Issue 548, eaap8608
DOI: 10.1126/scisignal.aap8608

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Converting transient to sustained signaling

Activation of fibroblast growth factor receptors (FGFRs) stimulates downstream signaling transiently because the receptors are endocytosed and degraded after activation. Nevertheless, FGFRs stimulate both sustained and transient ERK signaling. Fafilek et al. found that the inositol phosphatase SHIP2 was required for converting transient FGFR activation into sustained ERK signaling. The catalytic activity of SHIP2 was not required. Instead, SHIP2 acted as a scaffold that recruited Src family kinases to FGFR complexes, thus enhancing the phosphorylation of adaptor proteins that mediated signal relay from FGFRs to ERK. Because sustained ERK activation due to aberrant FGFR signaling is associated with oncogenesis and developmental disorders, SHIP2 may be a potential therapeutic target for these pathologies.