The Pathway for the Production of Inositol Hexakisphosphate in Human Cells
Affiliations
- PMID: 15531582
- DOI: 10.1074/jbc.M411528200
The yeast and Drosophila pathways leading to the production of
inositol hexakisphosphate (InsP(6)) have been elucidated recently. The
in vivo pathway in humans has been assumed to be similar. Here we show
that overexpression of Ins(1,3,4)P(3) 5/6-kinase in human cell lines
results in an increase of inositol tetrakisphosphate (InsP(4)) isomers,
inositol pentakisphosphate (InsP(5)) and InsP(6), whereas its depletion
by RNA interference decreases the amounts of these inositol phosphates.
Expression of Ins(1,3,4,6)P(4) 5-kinase does not increase the amount of
InsP(5) and InsP(6), although its depletion does block InsP(5) and
InsP(6) production, showing that it is necessary for production of
InsP(5) and InsP(6). Expression of Ins(1,3,4,5,6)P(5) 2-kinase increases
the amount of InsP(6) by depleting the InsP(5) in the cell, and
depletion of 2-kinase decreases the amount of InsP(6) and causes an
increase in InsP(5). These results are consistent with a pathway that
produces InsP(6) through the sequential action of Ins(1,3,4)P(3)
5/6-kinase, Ins(1,3,4,6)P(4) 5-kinase, and Ins(1,3,4,5,6)P5 2-kinase to
convert Ins(1,3,4)P(3) to InsP(6). Furthermore, the evidence implicates
5/6-kinase as the rate-limiting enzyme in this pathway.
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