Mutational analysis of cell cycle inhibition by integrin β(1C)

Jere E. Meredith, William B. Kiosses, Yoshikazu Takada, Martin Alexander Schwartz

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19 引文 斯高帕斯(Scopus)

摘要

Integrin β(1C) is an alternatively spliced cytoplasmic variant of the β1 subunit that potently inhibits cell cycle progression. In this study, we analyzed the requirements for growth suppression by β(1C). A chimera containing the extracellular/transmembrane domain of the Tac subunit of the human interleukin 2 receptor (gp55) fused to the cytoplasmic domain of β(1C) (residues 732-805) strongly inhibited growth in mouse 10T1/2 cells even at low expression levels, whereas chimeras containing the β(1A), β(1B), β(1D), β3, and β5 cytoplasmic domains had weak and variable effects. The β(1C) cytoplasmic domain is composed of a membrane proximal region (732- 757) common to all β1 variants and a COOH-terminal 48-amino acid domain (758-805) unique to β(1C) The β(1C)-specific domain (758-805) was sufficient to block cell growth even when expressed as a soluble cytoplasmic green fluorescent protein fusion protein. These results indicate that growth inhibition by β(1C) does not require the intact receptor and can function in the absence of membrane targeting. Analysis of deletions within the β(1C)- specific domain showed that the 18-amino acid sequence 775-792 is both necessary and sufficient for maximal growth inhibition, although the 13 COOH- terminal residues (793-805) also had weak activity. Finally, β(1C) is known to be induced in endothelial cells in response to tumor necrosis factor and is down-regulated in prostate epithelial cells after transformation. The green fluorescent protein/β(1C) (758-805) chimera blocked growth in the human endothelial cell line EV304 and in the transformed prostate epithelial cell line DU145, consistent with a role for β(1C) as a growth inhibitor in vivo.

原文英語
頁(從 - 到)8111-8116
頁數6
期刊Journal of Biological Chemistry
274
發行號12
DOIs
出版狀態已發佈 - 三月 19 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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