Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M006945200
Title: Evidence for Direct Interaction between Sprouty and Cbl
Authors: Wong, E.S.M.
Lim, J.
Low, B.C.
Chen, Q.
Guy, G.R. 
Issue Date: 23-Feb-2001
Citation: Wong, E.S.M., Lim, J., Low, B.C., Chen, Q., Guy, G.R. (2001-02-23). Evidence for Direct Interaction between Sprouty and Cbl. Journal of Biological Chemistry 276 (8) : 5866-5875. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M006945200
Abstract: Sprouty (SPRY) was first identified in a genetic screen in Drosophila as an antagonist of fibroblast and epidermal growth factor receptors and Sevenless signaling, seemingly by inhibiting the receptor tyrosine kinase (RTK)/Ras/MAPK pathway. To date, four mammalian Sprouty genes have been identified; the primary sequences of the gene products share a well conserved cysteine-rich C-terminal domain with their Drosophila counterpart. The N-terminal regions do not, however, exhibit a large degree of homology. This study was aimed at identifying proteins with which human SPRY2 (hSPRY2) interacts in an attempt to understand the mechanism by which Sprouty proteins exert their down-regulatory effects. Here, we demonstrate that hSPRY2 associates directly with c-Cbl, a known down-regulator of RTK signaling. A short sequence in the N terminus of hSPRY2 was found to bind directly to the Ring finger domain of c-Cbl. Parallel binding was apparent between the Drosophila homologs of Sprouty and Cbl, with cross-species associations occurring at least in vitro. Coexpression of hSPRY2 abrogated an increase in the rate of epidermal growth factor receptor internalization induced by c-Cbl, whereas a mutant hSPRY2 protein unable to bind c-Cbl showed no such effect. Our results suggest that one function of hSPRY2 in signaling processes downstream of RTKs may be to modulate c-Cbl physiological function such as that seen with receptor-mediated endocytosis.
Source Title: Journal of Biological Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/113470
ISSN: 00219258
DOI: 10.1074/jbc.M006945200
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

97
checked on Dec 12, 2018

WEB OF SCIENCETM
Citations

95
checked on Dec 12, 2018

Page view(s)

60
checked on Dec 14, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.