Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49414
Title: The Regulation of Sprouty by Casein Kinase 1
Authors: YIM GUO RONG DANIEL
Keywords: Growth factor signaling, Sprouty, Casein Kinase 1, neurite outgrowth, gastric cancer,
Issue Date: 16-Aug-2013
Source: YIM GUO RONG DANIEL (2013-08-16). The Regulation of Sprouty by Casein Kinase 1. ScholarBank@NUS Repository.
Abstract: Sprouty2 is a potent negative regulator of receptor tyrosine kinase signaling, and is implicated as a tumor suppressor. SPRY2 inhibits FGF-RAS-ERK signaling by binding to GRB2 during FGFR activation, disrupting the GRB2-SOS complex that transduces signals from FGFR to RAS. SPRY2 binding to GRB2 is modulated by phosphorylation but the key regulatory kinase(s) are not known. Prior studies identified the frequent presence of CK1 phosphorylation motifs on SPRY2. I therefore tested if CK1 plays a role in SPRY2 phosphorylation and function. Loss of CK1 binding, and inhibition of CK1 activity by two structurally distinct small molecules abrogated SPRY2 inhibition of FGF-ERK signaling, leading to decreased SPRY2 interaction with GRB2. Moreover, CK1 activity and binding are necessary for SPRY2 inhibition of FGF-stimulated neurite outgrowth in PC12 cells. Consistent with its proposed role as an inhibitor of FGF signaling, find that CSNK1E transcript abundance negatively correlates with FGF1/FGF7 message in human gastric cancer samples. Modulation of CK1 activity may be therapeutically useful in the treatment of FGF/SPRY2 related diseases.
URI: http://scholarbank.nus.edu.sg/handle/10635/49414
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Daniel Yim Thesis Final Submission.pdf9.94 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

130
checked on Dec 11, 2017

Download(s)

200
checked on Dec 11, 2017

Google ScholarTM

Check


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