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Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane.

The Journal of cell biology | 2005

Introduction of activated p21-activated kinase (PAK) is sufficient to release primary endothelial cells from contact inhibition of growth. Confluent cells display deficient activation of PAK and translocation of Rac to the plasma membrane at matrix adhesions. Targeting Rac to the plasma membrane rescues these cells from contact inhibition. PAK's ability to release human umbilical vein endothelial cells from contact inhibition is blocked by an unphosphorylatable form of its target Merlin, suggesting that PAK promotes mitogenesis by phosphorylating, and thus inactivating, Merlin. Merlin mutants, which are presumed to exert a dominant-negative effect, enable recruitment of Rac to matrix adhesions and promote mitogenesis in confluent cells. Small interference RNA-mediated knockdown of Merlin exerts the same effects. Dominant-negative Rac blocks PAK-mediated release from contact inhibition, implying that PAK functions upstream of Rac in this signaling pathway. These results provide a framework for understanding the tumor suppressor function of Merlin and indicate that Merlin mediates contact inhibition of growth by suppressing recruitment of Rac to matrix adhesions.

Pubmed ID: 16247032 RIS Download

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NCI NIH HHS, United States
    Id: R01 CA078901
  • Agency: NCI NIH HHS, United States
    Id: P30 CA08748
  • Agency: NCI NIH HHS, United States
    Id: R01 CA78901

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MERLIN (tool)

RRID:SCR_009289

Software application that carries out single-point and multipoint analyses of pedigree data, including IBD and kinship calculations, nonparametric and variance component linkage analyses, error detection and information content mapping. For multipoint analyses in dense maps, Merlin allows the user to impose constraints on the number of recombinants between consecutive markers. Merlin estimates haplotypes by finding the most likely path of gene flow or by sampling paths of gene flow at all markers jointly. It can also list all possible nonrecombinant haplotypes within short regions. Finally, Merlin provides swap-file support for handling very large numbers of markers as well as gene-dropping simulations for estimating empirical significance levels. (entry from Genetic Analysis Software)

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HUVEC-C (tool)

RRID:CVCL_2959

Cell line HUVEC-C is a Finite cell line with a species of origin Homo sapiens

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