Identifiers
HUGO:AKT1
HUGO:AKT1 HUGO:AKT2 HUGO:AKT3
AKT serine/threonine kinase 1
HUGO:AKT1 hgnc_id:HGNC:391 HGNC:391 ENTREZ:207 UNIPROT:P31749
AKT serine/threonine kinase 2
HUGO:AKT2 hgnc_id:HGNC:392 HGNC:392 ENTREZ:208 UNIPROT:P31751
AKT serine/threonine kinase 3
HUGO:AKT3 hgnc_id:HGNC:393 HGNC:393 ENTREZ:10000 UNIPROT:Q9Y243
v-akt murine thymoma viral oncogene homolog 1
HUGO:AKT1, HGNC:391, ENTREZ:207, UNIPROT:P31749
v-akt murine thymoma viral oncogene homolog 2
HUGO:AKT2, HGNC:392, ENTREZ:208, UNIPROT:P31751
v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma)
HUGO:AKT3, HGNC:393, ENTREZ:10000, UNIPROT:Q9Y243
HUGO:AKT1 HGNC:391 ENTREZ:207 UNIPROT:P31749 GENECARDS:AKT1 REACTOME:58253 KEGG:207 ATLASONC:AKT1ID355ch14q32 WIKI:AKT1
HUGO:AKT2 HGNC:392 ENTREZ:208 UNIPROT:P31751 GENECARDS:AKT2 REACTOME:49860 KEGG:208 ATLASONC:AKT2ID517ch19q13 WIKI:AKT2
HUGO:AKT3 HGNC:393 ENTREZ:10000 UNIPROT:Q9Y243 GENECARDS:AKT3 REACTOME:415917 KEGG:10000 ATLASONC:AKT3ID615ch1q44 WIKI:AKT3
HUGO:AKT3 HGNC:393 ENTREZ:10000 UNIPROT:Q9Y243 GENECARDS:AKT3 REACTOME:415917 KEGG:10000 ATLASONC:AKT3ID615ch1q44 WIKI:AKT3 HUGO:CDH2 HGNC:1759 ENTREZ:1000 UNIPROT:P19022 GENECARDS:CDH2 REACTOME:51212 KEGG:1000 ATLASONC:GC_CDH2 WIKI:CDH2

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
 Adaptive Immune Response   / TCR_SIGNALING 
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
 Cancer Associated Fibroblasts   / CORE 
HMC:SUSTAINING_PROLIFERATIVE_SIGNALLING
 Cell Cycle DNA Repair   / G1_S_CHECKPOINT 
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / FATTY_ACID_BIOSYNTHESIS 
 Regulated Cell Death   / GLUCOSE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / RCD_GENES 
 Innate Immunity   / IMMUNOSTIMULATORY_CORE_PATHWAYS 
HMC:EVADING_GROWTH_SUPPRESSORS
 Survival   / MAPK 
 Survival   / HEDGEHOG 
 Survival   / PI3K_AKT_MTOR 
 Survival   / WNT_NON_CANONICAL 

References
PMID:10625301 PMID:11532940
PMID:12670391 PMID:11135576 PMID:23087689 PMID:23732914 PMID:26552706 PMID:19406987 PMID:16962653 PMID:18566586
CASCADE:PDGF
PMID:11696562
Integrin-linked kinase (ILK) is a binding partner of the integrin 1 and 3 subunits and is involved in the signal transduction from integrin receptors
The activity is stimulated in a phosphatidylinositol (PI) 3-kinase???dependent manner and likely involves binding of the phosphoinositide phospholipid product of PI 3-kinase, PI 3,4,5-triphosphate, to the PH-like domain of ILK
ILK has been shown recently to directly phosphorylate proteins such as PKB (PKB/Akt) on ser 473.
PMID:27111285
ILK???PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast
PMID:25732845
Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression.
PMID:17397400
PDGF -receptor directly binds and activates PLC-gamma 1, RasGAP, P13K, and a 64 kd protein.
PI3K-Akt pathway promotes microtubule stabilization in migrating fibroblasts downstream of PDGF signaling
PMID:11747822
Akt but not SGK promotes cell motility downstream of the PI3-K-PDK1 pathway.
PMID:25924008
PMID:17604717
PMID:23030059
 MACROPHAGE 
 NATURAL_KILLER 
 NEUTROPHIL 
CASCADE:TGFB
CASCADE:LGALS3
CASCADE:IL4
CASCADE:IL15
CASCADE:IL21
CASCADE:CSF2
CASCADE:IFNG
PMID:22703233
TGFBR2 upregulates expression of markers M2 activation as ARG1, MCR2 and LGALS3 (galecsin3) and induces AKT activation.
PMID:18250477
Galectin-3 mediate alternative activation of macrophages via activation of PI3K signaling and AKT posphorylation. And regulates expression of MRC1 probably via PI3K
PMID:11687500
Binding to second messenger lipids allows PDK1 and AKT (PKB) to interact with each other, resulting in the phosphorylation and consequent activation of AKT (PKB).
PMID:24795729
IL15 induces IFNG production via PI3K/AKT/MTOR pathway.
PI3K???AKT???mTOR pathway is required for granzyme B production downstream of IL15.
Treatment with PI3K inhibitor abrogated the priming effect. Such inhibition was also observed
with blocking mTOR and AKT, downstream signaling components of PI3K pathway,
suggesting that PI3K???AKT???mTOR pathway is critical for optimal responses of ???primed??? NK cells to cytokine stimulations.
PMID:12906785, PMID:19022819
AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway.
PMID:19109239
IL4 induces he tyrosine phosphorylation of IRS-2 via Type I IL-4 Receptors. Activated IRS2 interacts with p85 subunit of PI3K and Grb2 and activates downstrean PI3K signaling (??phosphorylation of Akt on Ser473).
PMID:20805416
In differentiating moDCs, the PI3K/Akt-dependent mTOR pathway was constitutively activated by GM-CSF
And this signaling is needful for DC differentiation.
PMID:21826665
TLR4/PI3K /AKT signaling in TAN promotes motility of cancer cells
PMID:20214616
PMID:17680028
PMID:20398329

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / FATTY_ACID_BIOSYNTHESIS 
 Regulated Cell Death   / GLUCOSE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / RCD_GENES 

References
rc_re1706( Regulated Cell Death  ):
PMID:19203586
PHLDA3 competes with the PH domain of Akt for binding of membrane lipids, thereby inhibiting Akt translocation to the cellular membrane and activation
PMID:15718470
TORC2 complex as AKT S473 kinase
PMID:17604717
PDK1 phosphorylates the activation loop of AKT at T308

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / FATTY_ACID_BIOSYNTHESIS 
 Regulated Cell Death   / GLUCOSE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / RCD_GENES 

References
rc_re719:( Regulated Cell Death  ) reactionType:is.a
rc_re721:( Regulated Cell Death  ) PMID:12176997

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / FATTY_ACID_BIOSYNTHESIS 
 Regulated Cell Death   / GLUCOSE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / RCD_GENES 

References
rc_re721:( Regulated Cell Death  ) PMID:12176997

References
in_re1154( Innate Immunity  ):
PMID:16713974
AKT kinases phosphorylate GSK3 proteins and inhibit its activity downstream of TLR signaling.
IFNG prevents this inactivation.

References
su_mpk1_mpk1_re267( Survival  ):
PDK1 is a PI3K target leading to activation of P70 and subsequent cell growth. Signaling proteins with pleckstrin-homology (PH) domains accumulate at sites of PI3K activation by directly binding to PI(345)P3. Of particular interest are the protein serine-threonine kinases Akt and phosphoinositide-dependent kinase 1 (PDK1). Association with PI(345)P3 at the membrane brings these proteins into proximity and facilitates phosphorylation of Akt by PDK1. This phosphorylation stimulates the catalytic activity of Akt resulting in the phosphorylation of a host of other proteins that affect cell growth cell cycle entry and cell survival.
PMID:12040186

References
su_mpk1_mpk1_re267( Survival  ):
PDK1 is a PI3K target leading to activation of P70 and subsequent cell growth. Signaling proteins with pleckstrin-homology (PH) domains accumulate at sites of PI3K activation by directly binding to PI(345)P3. Of particular interest are the protein serine-threonine kinases Akt and phosphoinositide-dependent kinase 1 (PDK1). Association with PI(345)P3 at the membrane brings these proteins into proximity and facilitates phosphorylation of Akt by PDK1. This phosphorylation stimulates the catalytic activity of Akt resulting in the phosphorylation of a host of other proteins that affect cell growth cell cycle entry and cell survival.
PMID:12040186
su_mpk1_mpk1_re262( Survival  ):
JNK phosphorylates MST1 at serine 82 which leads to the enhancement of MST1 activation. The activation of MST1 phosphorylates FOXO3 at serine 207 and promotes cell death.
Phosphorylation of FOXO3 by Akt creates a binding site for the 14-3-3 family of proteins. The complex of FOXO3 and 14-3-3 is retained in the cytosol blocking transcription of genes normally stimulated by FOXO3.
PMID:20028971 PMID:12040186
su_mpk1_mpk1_re269( Survival  ):
P21 is a direct substrate of AKT and this may regulate the subcellular localisation of P21. Phosphorylation of P21 by AKT correlated with its exit from the nucleus and with increased cell cycle progression.
PMID:11882383
su_mpk1_mpk1_re270( Survival  ):
Akt phosphorylation of the apoptosis-inducing protein BAD creates a binding site for 14-3-3 proteins and prevents BAD from binding to Bcl-2 family members Bcl-2 and Bcl-XL thus releasing them for a cell survival response.
su_mpk1_mpk1_re271( Survival  ):
Glycogen synthase kinase 3 (GSK3) is a target of Akt. This protein kinase is constitutively active in unstimulated cells and phosphorylates many proteins (including glycogen synthase C-MYC and cyclin D) to keep them in inactive states or promote their degradation. Phosphorylation of GSK3 (both alpha and beta isoforms) by Akt turns off the catalytic activity of this enzyme resulting in the activation of pathways that are normally repressed by GSK3.
su_wnc1_s_wnc2_re4( Survival  ):
PMID:21506126, PMID:21303971
Path to phosphorylation of b-catenin is not completely depicted here. For full paths see AKT-pathway
Activated CaSR inhibits phosphorylation of b-catenin, exact mechanism unknown
PMID:22094462
su_wnc1_s_wnc2_re54:( Survival  ) PMID:18218901

References
s_akt2_re28( Survival  ):
PMID:16680151
PMID:20452955
PMID:19216069
s_akt2_re66:( Survival  ) PMID15169778
s_akt2_re89:( Survival  ) PMID:17646672
s_akt2_re113:( Survival  ) PMID:10217147
s_akt2_re144:( Survival  ) PMID:11463845 PMID:11756412
s_akt2_re152:( Survival  ) PMID:9829964

References
s_akt2_re28( Survival  ):
PMID:16680151
PMID:20452955
PMID:19216069

1. AKT*@Cytoplasm
2. AKT*|​pho@Cytoplasm
3. AKT*|​pho@Cytoplasm

1. AKT*@Cytosol
2. AKT*|​emp@Cytosol
3. AKT*|​pho@Cytosol
4. AKT*|​pho|​active@Cytosol
5. AKT*|​S473_pho|​T308_pho@Cytosol
6. AKT*|​S473_unk|​T308_unk@Cytosol
7. AKT*|​S473_unk|​T308_unk|​unfolded@Cytosol

1. AKT*@INNATE_IMMUNE_CELL_Cytosol
2. AKT*|​pho@INNATE_IMMUNE_CELL_Cytosol

1. AKT*@Nucleus
2. AKT*|​emp|​T450_pho|​pho@Nucleus
3. AKT*|​pho|​T450_pho|​pho|​active@Nucleus

1. AKT*@T_cell
2. AKT*|​Thr450_pho@T_cell
3. AKT*|​Thr308_pho|​Thr450_pho@T_cell
4. AKT*|​Thr308_pho|​ser473_pho|​Thr450_pho|​active@T_cell

1. AKT*|​pho|​pho:​PI3,4,5-P3@Cytosol
2. AKT*|​pho|​pho|​pho:​PI3,4,5-P3@Cytosol

1. AKT*|​Thr450_pho@T_cell → AKT*|​Thr308_pho|​Thr450_pho@T_cell
2. AKT*@T_cell → AKT*|​Thr450_pho@T_cell
3. AKT*|​Thr308_pho|​Thr450_pho@T_cell → AKT*|​Thr308_pho|​ser473_pho|​Thr450_pho|​active@T_cell
4. AKT*@T_cell → degraded
5. AKT*|​pho@Cytosol → Survival@Cytosol
6. AKT*|​emp@Cytosol → AKT*|​pho@Cytosol
7. AKT*|​pho@Cytosol → Survival@Cytosol
8. AKT*|​emp@Cytosol → AKT*|​pho@Cytosol
9. AKT*@Cytosol → AKT*|​pho|​active@Cytosol
10. AKT*|​pho|​active@Cytosol → MIGRATION_INTO_THE_TUMOR@default
11. AKT*@INNATE_IMMUNE_CELL_Cytosol → AKT*|​pho@INNATE_IMMUNE_CELL_Cytosol
12. AKT1@Cytosol → AKT*@Cytosol
13. AKT2@Cytosol → AKT*@Cytosol
14. AKT*@Cytosol → AKT*|​S473_pho|​T308_pho@Cytosol
15. AKT*|​S473_pho|​T308_pho@Cytosol → Necrosis death@Cytosol
16. AKT*@Cytosol → AKT*|​S473_pho|​T308_pho@Cytosol
17. AKT*|​S473_pho|​T308_pho@Cytosol → AKT*|​S473_unk|​T308_unk@Cytosol
18. AKT*@Cytosol → AKT*|​S473_unk|​T308_unk@Cytosol
19. AKT*|​S473_unk|​T308_unk@Cytosol → AKT*|​S473_unk|​T308_unk|​unfolded@Cytosol
20. AKT*|​pho|​T450_pho|​pho|​active@Nucleus → AKT*|​emp|​T450_pho|​pho@Nucleus
21. AKT*@Cytoplasm → AKT*|​pho@Cytoplasm
22. AKT*|​pho|​pho:​PI3,4,5-P3@Cytosol → AKT*|​pho|​pho|​pho:​PI3,4,5-P3@Cytosol
23. PI3K AKT MTOR pathway@Cytosol → AKT*|​pho|​pho:​PI3,4,5-P3@Cytosol

1. TSC1:​TSC2@T_cell → TSC1:​TSC2|​pho@T_cell
2. GSK3*@T_cell → GSK3*|​pho@T_cell
3. rCCND2@T_cell → CCND2@T_cell
4. rCCNE*@T_cell → CCNE*@T_cell
5. rCDKN1B@T_cell → CDKN1B@T_cell
6. GDP:​RAF1@Cytosol → GDP:​RAF1|​pho@Cytosol
7. NOS3|​S1179_emp@Cytosol → NOS3|​S1179_pho@Cytosol
8. FOXO1@Cytosol → FOXO1|​pho@Cytosol
9. BAD@Cytosol → BAD|​pho@Cytosol
10. Caspase9*@Cytosol → Caspase9*|​pho@Cytosol
11. gSurvivin*@Nucleus → rSurvivin*@Nucleus
12. CCDC88A@Cytosol → CCDC88A|​pho@Cytosol
13. Alpha_tubulin*:​Beta-tubulin*@Cytosol → Microtubule_polymerization@Cytosol
14. ETS2@Cytosol → ETS2|​pho|​active@Cytosol
15. rACTA2@Cytosol → ACTA2@Cytosol
16. FOXO*|​unk@Nucleus → FOXO*@Nucleus
17. GSK3_beta_*@INNATE_IMMUNE_CELL_Cytosol → GSK3_beta_*|​pho@INNATE_IMMUNE_CELL_Cytosol
18. GSK3_alpha_*@INNATE_IMMUNE_CELL_Cytosol → GSK3_alpha_*|​pho@INNATE_IMMUNE_CELL_Cytosol
19. TSC1:​TSC2@INNATE_IMMUNE_CELL_Cytosol → TSC1:​TSC2|​pho@INNATE_IMMUNE_CELL_Cytosol
20. p27KIP1*@Nucleus → p27KIP1*|​T198_pho|​T157_pho@Nucleus
21. BAX@Cytosol → BAX|​S184_pho@Cytosol
22. rHIF1A@Nucleus → HIF1A@Cytosol
23. ACLY@Cytosol + ATP@Cytosol → ACLY|​S454_pho@Cytosol + ADP@Cytosol
24. GSK3_beta_*@Cytosol → GSK3_beta_*|​S9_pho@Cytosol
25. GSK3_alpha_*@Cytosol → GSK3_alpha_*|​S21_pho@Cytosol
26. FOXO*@Cytosol → FOXO*|​pho|​pho@Cytosol
27. TSC1:​TSC2|​M1_unk@Cytosol → TSC1:​TSC2|​pho|​T1462_pho|​M1_unk@Cytosol
28. rc_s5506 → rc_s5649
29. BimEL*@Cytosol → BimEL*|​S87_pho@Cytosol
30. SNAP23:​STX4:​STXBP4@Cytosol → STXBP4|​S99_pho@Cytosol + SNAP23:​STX4@Cytosol
31. SLC2A1@Secretory Granule → SLC2A1@Cytosol
32. XIAP@Cytosol → XIAP|​S87_pho@Cytosol
33. Caspase9*|​T125_unk|​S144_unk|​Y153_unk@Cytosol → Caspase9*|​S196_pho|​T125_unk|​S144_unk|​Y153_unk@Cytosol
34. BAD@Cytosol → BAD|​pho@Cytosol
35. FOXO4@Nucleus → FOXO4|​T28_pho|​S193_pho|​S258_pho@Nucleus
36. p21CIP1*@Nucleus → p21CIP1*|​pho@Nucleus
37. p21CIP1*|​pho@Nucleus → p21CIP1*|​pho|​pho@Nucleus
38. CREB*@Nucleus → CREB*|​pho@Nucleus
39. FOXO1@Nucleus → FOXO1|​T24_pho|​S256_pho|​S319_pho@Nucleus
40. FOXO3|​pho:​promoter_region@Nucleus → FOXO3|​pho|​pho|​pho:​promoter_region@Nucleus
41. MDM2|​pho|​pho@Nucleus → MDM2|​pho|​pho|​pho@Nucleus
42. su_akt1_s_akt2_s228 → FOXO1|​T24_pho|​S256_pho|​S319_pho:​promoter_region@Nucleus
43. FOXO3@Cytoplasm → FOXO3|​pho@Nucleus
44. p21CIP1*@Nucleus → p21CIP1*|​pho@Cytoplasm
45. su_mpk1_mpk1_s953 → BCL2@Mitochondria + BAD@Mitochondria
46. GSK3_beta_*@Cytoplasm → GSK3_beta_*|​pho@Cytoplasm
47. AKAP*:​PKA*@Primary Cilium → PKA*@Primary Cilium + AKAP*@Primary Cilium
48. GSK3_beta_*@Cytosol → GSK3_beta_*|​pho|​active@Cytosol
49. _beta_-Catenin*@Cytoplasm → _beta_-Catenin*|​S552_pho@Cytoplasm
50. HOMER3@Cytoplasm → HOMER3|​T36_pho|​S38_pho|​S52_pho@Cytoplasm
51. HSP90*|​hm2:​PTGES3:​TERT@Cytosol → HSP90*|​hm2:​PTGES3:​TERT|​S227_pho@Cytosol