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PI3-Kinase Pathway
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PI3-Kinase, Lipid Binding Domains, Regulation of fork head localisation, Signalling Growth.
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Cells and ImmunityWeek 4
Mike Fry
PI3- Kinases [PKB/Akt] Pathway
- PI3 Kinase = protein kinase B = Akt
- [PI] = phosphatidylinositol [inner leaflet on membrane phospholipid]
- Cell survival signals in from growth factors or cell-cell and cell matrix via intrigrins
- PI3Kinases discovered in 1980’s linked to many pathways, mainly research was done
on 2 inhibitors; fungal metabolite Wortmannin [WORT] and a product LY294002
which both inhibit PI3K.
o Activators; fMLP/Cytokines/Calcium/Insulin/Growth Factors/ Thrombin/
Integrins/ B&T cell activators
o Function; oncogenic transformation/ regulation of cytoskeleton / differential /
survival / secretion / migration / chemotaxis/ oxidation bursts / insulin-
stimulated glucose uptake / protein trafficking.
- PI3-Kinase;
o Inner leaflet of lipid bilayer;
diacylglycerol
o phosphodiester link.
o In cytosol; inositol head group
o PIK3; phosphorylate HO at position 3
o PIK4; position 4 // PIK5; position 5
o Position 2, 6 unavailable to bind.
Class IA PI3K activated by protein tyrosine kinases [P110αβδ +
p85αβγ]
Class IB PI3K activated by GPCR [p110γ + p101]
Class I phosphorylates if 4/5 already done
Class II PI3K [phosphorylates p3 and p4] // Class III PI3K [only
phosphorylates 3 only if others are not phosphorylated]
- Lipid Binding Domains;
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