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- W4205148085 abstract "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. PMID: 16247032 Funding information This work was supported by: NCI NIH HHS, United States Grant ID: R01 CA78901 NCI NIH HHS, United States Grant ID: P30 CA08748" @default.
- W4205148085 created "2022-01-26" @default.
- W4205148085 creator A5000246031 @default.
- W4205148085 date "2006-01-04" @default.
- W4205148085 modified "2023-10-16" @default.
- W4205148085 title "Faculty Opinions recommendation of Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane." @default.
- W4205148085 doi "https://doi.org/10.3410/f.1026188.355420" @default.
- W4205148085 hasPublicationYear "2006" @default.
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