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Sensitization of epidermal growth factor-induced signaling by bradykinin is mediated by c-Src - Implications for a role of lipid microdomains SCIE SCOPUS

Title
Sensitization of epidermal growth factor-induced signaling by bradykinin is mediated by c-Src - Implications for a role of lipid microdomains
Authors
Hur, EMPark, YSLee, BDJang, IHKim, HSKim, TDSuh, PGRyu, SHKim, KT
Date Issued
2004-02-13
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLO
Abstract
Communication between receptor tyrosine kinase (RTK)- and G protein-coupled receptor (GPCR)- mediated signaling systems has received increasing attention in recent years. Here, we report that activation of G protein-coupled bradykinin B-2 receptor induces an up-regulation of cellular responses mediated by epidermal growth factor receptor (EGFR) and provide essential mechanistic characteristics of this sensitization process. EGF, which failed to evoke detectable amount of calcium increase and neurotransmitter release when administrated alone in primary cultures of rat adrenal chromaffin cells and PC12 cells, became capable of inducing these responses specifically after bradykinin pretreatment. Both EGFR and non-receptor tyrosine kinase p60(Src), whose kinase activities were required in the sensitization, were found to be enriched in cholesterolrich lipid rafts. Bradykinin caused activation of p60(Src) and Src-dependent phosphorylation of the EGFR on Tyr-845 in lipid rafts, as well as recruitment of phospholipase C (PLC) gamma1 to the rafts. Depletion of cholesterol by methyl-beta-cyclodextrin disrupted the raft localization of EGFR and Src, as well as bradykinin-induced translocation of PLCgamma1. Furthermore, sensitization, which was impaired by cholesterol depletion, was restored by repletion of cholesterol. Therefore, we suggest that lipid rafts are essential participants in the regulation of receptor-mediated signal transduction and cross-talk via organizing signaling complexes in membrane microdomains.
Keywords
FACTOR RECEPTOR TRANSACTIVATION; PROTEIN-COUPLED RECEPTORS; ADRENAL CHROMAFFIN CELLS; SMOOTH-MUSCLE-CELLS; PLASMA-MEMBRANE; TYROSINE PHOSPHORYLATION; ACTION-POTENTIALS; ERK ACTIVATION; CALCIUM-ENTRY; CELLULAR SRC
URI
https://oasis.postech.ac.kr/handle/2014.oak/18102
DOI
10.1074/jbc.M311687200
ISSN
0021-9258
Article Type
Article
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279, no. 7, page. 5852 - 5860, 2004-02-13
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류성호RYU, SUNG HO
Dept of Life Sciences
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