an effect previously noted by other groups
signal can be transduced by
the actions of a PtdIns(3,4,5)P
protein kinase; thus, the regulation of this
pathway is analogous to that of other sig
naling systems that respond to small mole
cule signals (adenosine 3
phate–dependent protein kinase, protein ki
nase C, and Ca
protein kinases). In the PtdIns(3,4,5)P
pathway, the lipid signal controls PKB ac
tivity in two distinct but cooperative ways,
which is reminiscent of the role of adeno
sine monophosphate (AMP) to allosterical
ly activate the AMP
activated protein ki
nase, and also to activate the kinase that
phosphorylates the AMP
). This may ensure tight regulation of
PKB at the correct membrane localization,
and it will be interesting to see whether this
dual regulatory principle will apply to other
targets in the PI3K signaling pathway.
Note added in proof
: A PtdIns(3,4,5)P
dependent protein kinase has been purified
) that may be related to the upstream
kinase described here.
REFERENCES AND NOTES
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16. PSG5(HA)PKB was obtained from B. Burgering (Utre-
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with a strategy based on the polymerase chain reaction
[with the use of
DNA polymerase (Stratagene) and
low cycle numbers]. The
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first 125 amino acids. All mutations were checked by
sequencing. The appropriate cDNAs were then sub-
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(Glu-Glu) tags (
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17. D. Stokoe, unpublished data.