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- W2113167811 abstract "Few molecular events important to platelet biogenesis have been identified. Mice homozygous for the spontaneous, recessive mutation gunmetal (gm) have prolonged bleeding, thrombocytopenia, and reduced platelet alpha- and delta-granule contents. Here we show by positional cloning that gm results from a G-->A substitution mutation in a splice acceptor site within the alpha-subunit of Rab geranylgeranyl transferase (Rabggta), an enzyme that attaches geranylgeranyl groups to Rab proteins. Most Rabggta mRNAs from gm tissues skipped exon 1 and lacked a start codon. Rabggta protein and Rab geranylgeranyl transferase (GGTase) activity were reduced 4-fold in gm platelets. Geranylgeranylation and membrane association of Rab27, a Rab GGTase substrate, were significantly decreased in gm platelets. These findings indicate that geranylgeranylation of Rab GTPases is critical for hemostasis. Rab GGTase inhibition may represent a new treatment for thrombocytosis and clotting disorders." @default.
- W2113167811 created "2016-06-24" @default.
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- W2113167811 date "2000-03-28" @default.
- W2113167811 modified "2023-10-12" @default.
- W2113167811 title "Rab geranylgeranyl transferase α mutation in the <i>gunmetal</i> mouse reduces Rab prenylation and platelet synthesis" @default.
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- W2113167811 doi "https://doi.org/10.1073/pnas.080517697" @default.
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