Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2

Prasenjit Mitra, Asit De, Michael F. Ethier, Koshi Mimori, Karen Kodys, Kenji Shibuta, Masaki Mori, J. Mark Madison, Carol Miller-Graziano, Graham F. Barnard

研究成果: ジャーナルへの寄稿記事

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Expression of the chemokine stromal cell-derived factor-1α (SDF-1α) is absent from many carcinomas, including hepatomas. We note an early signalling defect in the hepatocellular carcinoma (HCC) cell line HepG2 that expresses the CXCR4 receptor and binds biotin-labelled SDF, but fails to stimulate downstream signalling events after engagement with SDF. In HepG2, the SDF/CXCR4 interaction did not result in calcium influx, phosphorylation and internalization of CXCR4, nor in a rapid phosphorylation of p44/42 MAP kinase. There were no CXCR4 mutations in the second chemokine binding loop or C terminal phosphorylation and internalization domains. The downstream signalling machinery in HepG2 appears to be intact since transfection of wild-type CXCR4 restored functional responsiveness. We conclude that HepG2 is unresponsive to SDF stimulation because of a defect located after receptor binding but before the activation of the signalling cascade. A hypothetical blocking molecule could hinder receptor internalization or CXCR4 signalling.

元の言語英語
ページ(範囲)311-319
ページ数9
ジャーナルCellular Signalling
13
発行部数5
DOI
出版物ステータス出版済み - 5 1 2001

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All Science Journal Classification (ASJC) codes

  • Cell Biology

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