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Title: Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling
Authors: Wong, E.S.M.
Fong, C.W.
Lim, J.
Yusoff, P.
Low, B.C. 
Langdon, W.Y.
Guy, G.R. 
Keywords: C-Cbl
Issue Date: 16-Sep-2002
Citation: Wong, E.S.M., Fong, C.W., Lim, J., Yusoff, P., Low, B.C., Langdon, W.Y., Guy, G.R. (2002-09-16). Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling. EMBO Journal 21 (18) : 4796-4808. ScholarBank@NUS Repository.
Abstract: Drosophila Sprouty (dSpry) was genetically identified as a novel antagonist of fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and Sevenless signalling, ostensibly by eliciting its response on the Ras/MAPK pathway. Four mammalian sprouty genes have been cloned, which appear to play an inhibitory role mainly in FGF-mediated lung and limb morphogenesis. Evidence is presented herein that describes the functional implications of the direct association between human Sprouty2 (hSpry2) and c-Cbl, and its impact on the cellular localization and signalling capacity of EGFR. Contrary to the consensus view that Spry2 is a general inhibitor of receptor tyrosine kinase signalling, hSpry2 was shown to abrogate EGFR ubiquitylation and endocytosis, and sustain EGF-induced ERK signalling that culminates in differentiation of PC12 cells. Correlative evidence showed the failure of hSpry2ΔN11 and mSpry4, both deficient in c-Cbl binding, to instigate these effects. hSpry2 interacts specifically with the c-Cbl RING finger domain and displaces UbcH7 from its binding site on the E3 ligase. We conclude that hSpry2 potentiates EGFR signalling by specifically intercepting c-Cbl-mediated effects on receptor down-regulation.
Source Title: EMBO Journal
ISSN: 02614189
DOI: 10.1093/emboj/cdf493
Appears in Collections:Staff Publications

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