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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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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

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Title
Sensitization of epidermal growth factor-induced signaling by bradykinin is mediated by c-Src - Implications for a role of lipid microdomains
Author
Hur, EMPark, YSLee, BDJang, IHKim, HSKim, TDSuh, Pann-GhillRyu, SHKim, KT
Issue Date
2004-02
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.279, no.7, pp.5852 - 5860
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
URI
https://scholarworks.unist.ac.kr/handle/201301/16441
DOI
10.1074/jbc.M311687200
ISSN
0021-9258
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