Table 1.

Characteristics and Experimental Evidence for a Subset of Akt Substrates^a

			In Vivod
Target	Human Site(s)b	In Vitroc	W/L	LOF	GOF	Genetic Evidencee	Regulatory Effect?f
FOXO1	T24, S256, S319	+	+	+	+	M, F, W	Inhibit
FOXO3A	T32, S253, S315	+	+	+	+	M, F, W	Inhibit
FOXO4	T32, S197, S262	+	+	+	+	M, F, W	Inhibit
TSC2	S939, T1462	+	+	+	+	M, F	Inhibit
GSK3α/β	S21/S9	+	+	+	+	M	Inhibit
RAF1	S259	+	+	+	+	−	Inhibit
PRAS40	T246	+	+	−	+	M	Inhibit
AS160	S588, T642	+	+	−	+	−	Inhibit
BAD	S99	+	+	+	+	−	Inhibit
WNK1	T60	+	+	+	+	M	?
MDM2	S166, S186	+	+	+	+	−	Activate
Chk1	S280	+	+	+	+	M	Inhibit
eNOS	S1177	+	+	+	+	M	Activate
ASK1	S83	+	+	+	+	−	Inhibit
IKKα	T23	+	−	−	+	−	Activate
P21CIP1	T145	+	+	+	+	−	Inhibit
p27KIP1	T157	+	+	+	+	−	Inhibit
Casp9	S196	+	−	+	+	−	Inhibit

^aFor an expanded version of this table see Table S1.

^bHuman numbering of sites with strongest evidence of being phosphorylated by Akt in vivo.

^cDirect phosphorylation of the given site(s) with purified Akt and full-length substrate in vitro.

^dEvidence of Akt-dependent phosphorylation of the given site(s) within cells (− means no published evidence), including: W/L, sensitivity to PI3K inhibition using ≤ 100 nM wortmannin (W) and/or ≤ 20 μM LY294002 (L); LOF, loss-of-AKT-function evidence using dominant-negative mutants and/or RNAi approaches; GOF, gain-of-Akt-function evidence using overexpression and/or constitutively active mutants.

^eGenetic evidence in model organisms, including epistasis analyses in Drosophila (F) or C. elegans (W) or loss-of-phosphorylation in mouse mutants (M) lacking Akt function.

^fFunctional consequence of Akt-mediated phosphorylation.