期刊
JOURNAL OF BIOCHEMISTRY
卷 145, 期 1, 页码 21-30出版社
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvn137
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资金
- Ministerio de Ciencia y Tecnologia [PB1998-12]
- Plan Andaluz de Investigacion [PAI-2003-04]
- Fundacion Marcelino Botin, Spain.
To dissect the rat receptor for advanced glycation end products (RAGE) subcellular distribution and trafficking in eukaryotic cells, an expression system coding for a fusion protein between the RAGE and an enhanced green fluorescent protein (EGFP) has been used. The RAGEEGFP protein is expressed at the plasma membrane of CHO-k1 and Neuro-2a (N2a) cells and retains the capacity to bind Texas Red-labelled advanced glycation end products (AGEs). AGEs addition to the cell cultures induced a change in the subcellular distribution of the fluorescent RAGEEGFP protein compatible with an internalization of the AGEsRAGE complex. Furthermore, while N2a cells expressing the RAGEEGFP showed an increase in ERK1/2 phosphorylation and NF-B DNA binding in response to AGEs, pre-incubation with dansyl-cadaverine or phenylarsine oxide, inhibitors of receptors internalization, blocked the activation of ERKs and other intracellular responses mediated by AGEs. These results suggest that internalization plays a key role in the signal transduction mediated by RAGE.
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