Phosphoinositide 3-kinases (PI 3-kinases) are an evolutionarily conserved family of lipid kinases that have attracted much attention over the past 10 years or so (reviewed in ref.
1
). Three PI 3-kinase classes have been defined on the basis of primary structure, regulation, and their in vitro lipid substrate specificity. Class I PI 3-kinases interact with Ras and form heterodimeric complexes with adaptor proteins that link them to different upstream signaling events (
1
). They are able to convert phosphatidylinositol (PtdIns), PtdIns(
4
)
P
, and PtdIns(
4
,
5
)
P
2
into PtdIns(
3
)
P
, PtdIns(
3
,
4
)
P
2
, and PtdIns(
3
,
4
,
5
)
P
3
, respectively, by phosphorylating the D-3 position of the inositol head groups of phosphoinositide lipids (collectively known as D-3 phosphoinositide lipids and shown in Fig. 1 ) (
1
,
2
).
Fig. 1.
(
A
) Schematic representation of the structure of D-3 phosphoinositide lipids. (
B
) Routes for synthesis of PtdIns(
3
)
P
, PtdIns(
3
,
5
)
P
2
, PtdIns(
3
,
4
)
P
2
, and PtdIns(
3
,
4
,
5
)
P
3
.