Protein AKT
PMID:18215152
PMID:17141160
PMID:16962829
PMID:17043309
PMID:10801415
Activation of AKT by mTORC2 and PDK1:
From Jacinto, 2008 (PMID:18215152); In vivo analyses also support mTORC2 as a critical regulator of HM phosphorylation. Knockdown of the mTORC2 component rictor, but not the mTORC1 component raptor, led to defective phosphorylation of Akt at Ser473 [39]. This decrease in Ser473 phosphorylation was also accompanied by defective Thr308 phosphorylation, in agreement with previous claims that Ser473 phosphorylation is important for subsequent Thr308 phosphorylation [168,176,177]. Genetic studies using MEFs from mice that have deficient mTORC components confirm that mTORC2 is required for HM site phosphorylation. In rictor-, mLST8- or SIN1-knockout cells, Ser473 phosphorylation was abolished. Phosphorylation at Thr308 was not grossly abnormal in rictor-/- cells [51,52] and was normal in mLST8-/- [27] and in SIN1-/- cells [40]. These findings support the alternative view that PDK1 docking to the phosphorylated HM site of Akt is not critical for T-loop phosphorylation (see also S6K and PKC). Studies from PDK1-/- ES cells have also revealed that in the absence of Thr308 phosphorylation, the HM site phosphorylation at Ser473 still occurs [146]. Thus phosphorylation of the T-loop and HM site of Akt seems to occur independently of each other. Akt remained partly active in mTORC2-disrupted cells and phosphorylated a subset of its known substrates but was defective in the phosphorylation of the apoptosis promoting proteins Foxo1/3a [40]. These findings suggest that the phosphorylation of Ser473 may play a role in cell survival and that HM site phosphorylation may regulate substrate specificity in Akt and possibly other AGC kinases as well.
Modifications:
In compartment: Cell membrane
- AKT@Cell membrane
- AKT|T450_pho@Cell membrane
- AKT|T450_pho@Cell membrane
- AKT|S473_pho|T450_pho|active@Cell membrane
Participates in complexes:
In compartment: Cell membrane
- AKT:HSP90@Cell membrane
- AKT:PI3,4,5-P_sub_3@Cell membrane
- AKT|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- AKT|S473_pho|T450_pho:Sin1.1@Cell membrane
- AKT|S473_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- AKT|T308_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- AKT|T308_pho|S473_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
Participates in reactions:
As Reactant or Product:- AKT|T450_pho:PI3,4,5-P_sub_3@Cell membrane
→
AKT|S473_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- AKT|T450_pho@Cell membrane
→
AKT|T450_pho@Cell membrane
- AKT|T450_pho@Cell membrane
+ PI3,4,5-P_sub_3@Cell membrane
→
AKT|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- AKT|S473_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
→
AKT|T308_pho|S473_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- PDGF:PDGFR_beta@Cell membrane
→
AKT|T308_pho|S473_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- AKT|T450_pho:PI3,4,5-P_sub_3@Cell membrane
→
AKT|S473_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- AKT|T450_pho:PI3,4,5-P_sub_3@Cell membrane
→
AKT|T308_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
- rAKT@Cell membrane
→
AKT@Cell membrane
- AKT@Cell membrane
→
AKT|T450_pho@Cell membrane
- AKT@Cell membrane
→
degraded
- HSP90@Cell membrane
+ AKT@Cell membrane
→
AKT:HSP90@Cell membrane
- AKT|T450_pho@Cell membrane
→
AKT|S473_pho|T450_pho|active@Cell membrane
- AKT|S473_pho|T450_pho|active@Cell membrane
+ Sin1.1@Cell membrane
→
AKT|S473_pho|T450_pho:Sin1.1@Cell membrane
- AKT|S473_pho|T450_pho|active@Cell membrane
→
AKT|T450_pho@Cell membrane
- AKT|T308_pho|S473_pho|T450_pho:PI3,4,5-P_sub_3@Cell membrane
→
AKT:PI3,4,5-P_sub_3@Cell membrane
As Catalyser:- TSC2|S1798_pho@Nucleus
→
TSC2|S981_pho|S939_pho|S1798_pho|T1462_pho@Cell membrane
- GSK3alpha/beta@Cell membrane
→
GSK3alpha/beta|S21/9_pho@Cell membrane
- TSC1:TSC2@Endomembrane
→
TSC1:TSC2|S981_pho|S939_pho|T1462_pho@Endomembrane
- PRAS40:mTORC1@Cell membrane
→
PRAS40|T246_pho:mTORC1@Cell membrane
- AKT@Cell membrane
→
degraded
- FoxO1/3a@Nucleus
→
FoxO1/3a|S253_pho|T24/32_pho@Nucleus
- p27|S10_pho@Cell membrane
→
p27|S10_pho|T198_pho@Cell membrane
- p27|S10_pho|T198_pho@Cell membrane
→
p27|S10_pho|T198_pho|T157_pho@Cell membrane
- Mdm2@Cell membrane
→
Mdm2|pho@Cell membrane