Phospho-pan-AKT1/2/3 (Thr308) Antibody - #AF3262
产品描述
*The optimal dilutions should be determined by the end user.
*Tips:
WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.
引用格式: Affinity Biosciences Cat# AF3262, RRID:AB_2834688.
展开/折叠
AKT 1; AKT; AKT1; AKT1_HUMAN; MGC99656; PKB; PKB-ALPHA; PRKBA; Protein Kinase B Alpha; Protein kinase B; Proto-oncogene c-Akt; RAC Alpha; RAC; RAC-alpha serine/threonine-protein kinase; RAC-PK-alpha; Akt2; AKT2_HUMAN; HIHGHH; murine thymoma viral (v-akt) homolog-2; PKB; PKB beta; PKBB; PKBBETA; PRKBB; Protein kinase Akt 2; Protein kinase Akt-2; Protein kinase B beta; rac protein kinase beta; RAC-BETA; RAC-beta serine/threonine-protein kinase; RAC-PK-beta; v akt murine thymoma viral oncogene homolog 2; Akt3; AKT3 kinase; AKT3_HUMAN; DKFZp434N0250; MPPH; PKB gamma; PKBG; PRKBG; Protein kinase Akt-3; Protein Kinase AKT3; Protein kinase B gamma; RAC gamma; RAC gamma serine/threonine protein kinase; RAC-gamma serine/threonine-protein kinase; RAC-PK-gamma; RACPK Gamma; Serine threonine protein kinase Akt 3; Serine threonine protein kinase Akt3; STK 2; STK-2; STK2; V akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma); V akt murine thymoma viral oncogene homolog 3; V akt murine thymoma viral oncogene homolog 3 protein kinase B gamma;
抗原和靶标
Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Expressed in all human cell types so far analyzed. The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages.
P31751 AKT2_HUMAN:Expressed in all cell types so far analyzed.
Q9Y243 AKT3_HUMAN:In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.
- P31749 AKT1_HUMAN:
- Protein BLAST With
- NCBI/
- ExPASy/
- Uniprot
MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA
- P31751 AKT2_HUMAN:
- Protein BLAST With
- NCBI/
- ExPASy/
- Uniprot
MNEVSVIKEGWLHKRGEYIKTWRPRYFLLKSDGSFIGYKERPEAPDQTLPPLNNFSVAECQLMKTERPRPNTFVIRCLQWTTVIERTFHVDSPDEREEWMRAIQMVANSLKQRAPGEDPMDYKCGSPSDSSTTEEMEVAVSKARAKVTMNDFDYLKLLGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGELFFHLSRERVFTEERARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGISDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFPRTLSPEAKSLLAGLLKKDPKQRLGGGPSDAKEVMEHRFFLSINWQDVVQKKLLPPFKPQVTSEVDTRYFDDEFTAQSITITPPDRYDSLGLLELDQRTHFPQFSYSASIRE
- Q9Y243 AKT3_HUMAN:
- Protein BLAST With
- NCBI/
- ExPASy/
- Uniprot
MSDVTIVKEGWVQKRGEYIKNWRPRYFLLKTDGSFIGYKEKPQDVDLPYPLNNFSVAKCQLMKTERPKPNTFIIRCLQWTTVIERTFHVDTPEEREEWTEAIQAVADRLQRQEEERMNCSPTSQIDNIGEEEMDASTTHHKRKTMNDFDYLKLLGKGTFGKVILVREKASGKYYAMKILKKEVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGGELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGITDAATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDIKFPRTLSSDAKSLLSGLLIKDPNKRLGGGPDDAKEIMRHSFFSGVNWQDVYDKKLVPPFKPQVTSETDTRYFDEEFTAQTITITPPEKYDEDGMDCMDNERRPHFPQFSYSASGRE
种属预测
score>80的预测可信度较高,可尝试用于WB检测。*预测模型主要基于免疫原序列比对,结果仅作参考,不作为质保凭据。
High(score>80) Medium(80>score>50) Low(score<50) No confidence
翻译修饰 - P31749/P31751/Q9Y243 作为底物
Site | PTM Type | Enzyme | Source |
---|---|---|---|
S2 | Phosphorylation | Uniprot | |
K8 | Ubiquitination | Uniprot | |
K14 | Acetylation | Uniprot | |
K14 | Methylation | Uniprot | |
K14 | Ubiquitination | Uniprot | |
K20 | Acetylation | Uniprot | |
K20 | Ubiquitination | Uniprot | |
K30 | Ubiquitination | Uniprot | |
T34 | Phosphorylation | O15530 (PDPK1) , Q05513 (PRKCZ) | Uniprot |
K39 | Ubiquitination | Uniprot | |
T65 | Phosphorylation | Uniprot | |
T72 | Phosphorylation | P31749 (AKT1) | Uniprot |
T87 | Phosphorylation | Uniprot | |
T92 | Phosphorylation | Uniprot | |
S122 | Phosphorylation | Uniprot | |
S124 | Phosphorylation | Uniprot | |
S126 | O-Glycosylation | Uniprot | |
S126 | Phosphorylation | Uniprot | |
S129 | O-Glycosylation | Uniprot | |
S129 | Phosphorylation | P68400 (CSNK2A1) | Uniprot |
S137 | Phosphorylation | Uniprot | |
K140 | Ubiquitination | Uniprot | |
T146 | Phosphorylation | Uniprot | |
K154 | Ubiquitination | Uniprot | |
K158 | Ubiquitination | Uniprot | |
T172 | Phosphorylation | Uniprot | |
Y176 | Phosphorylation | Q07912 (TNK2) | Uniprot |
K189 | Ubiquitination | Uniprot | |
T211 | Phosphorylation | Uniprot | |
S216 | Phosphorylation | Uniprot | |
C224 | S-Nitrosylation | Uniprot | |
S246 | Phosphorylation | P31749 (AKT1) | Uniprot |
S259 | Phosphorylation | Uniprot | |
K268 | Ubiquitination | Uniprot | |
K276 | Sumoylation | Uniprot | |
K276 | Ubiquitination | Uniprot | |
K284 | Ubiquitination | Uniprot | |
K289 | Ubiquitination | Uniprot | |
T291 | Phosphorylation | Uniprot | |
C296 | S-Nitrosylation | Uniprot | |
K297 | Ubiquitination | Uniprot | |
K301 | Sumoylation | Uniprot | |
K301 | Ubiquitination | Uniprot | |
T305 | O-Glycosylation | Uniprot | |
T305 | Phosphorylation | Uniprot | |
T308 | O-Glycosylation | Uniprot | |
T308 | Phosphorylation | P31749 (AKT1) , P17252 (PRKCA) , Q9UHD2 (TBK1) , P05771 (PRKCB) , Q15139 (PRKD1) , Q8N5S9 (CAMKK1) , Q14164 (IKBKE) , Q07912 (TNK2) , P78527 (PRKDC) , O15530 (PDPK1) | Uniprot |
C310 | S-Nitrosylation | Uniprot | |
T312 | O-Glycosylation | Uniprot | |
T312 | Phosphorylation | P49840 (GSK3A) | Uniprot |
Y315 | Phosphorylation | Q13882 (PTK6) , P12931 (SRC) , P07949 (RET) | Uniprot |
Y326 | Phosphorylation | P12931 (SRC) , Q13882 (PTK6) | Uniprot |
K377 | Ubiquitination | Uniprot | |
S378 | Phosphorylation | Uniprot | |
S396 | Phosphorylation | Uniprot | |
K400 | Ubiquitination | Uniprot | |
Y417 | Phosphorylation | Uniprot | |
K420 | Acetylation | Uniprot | |
K426 | Acetylation | Uniprot | |
K426 | Ubiquitination | Uniprot | |
T435 | Phosphorylation | Uniprot | |
Y437 | Phosphorylation | Uniprot | |
T443 | Phosphorylation | Uniprot | |
T448 | Phosphorylation | Uniprot | |
T450 | Phosphorylation | P42345 (MTOR) | Uniprot |
S457 | Phosphorylation | Uniprot | |
S473 | O-Glycosylation | Uniprot | |
S473 | Phosphorylation | P05771 (PRKCB) , Q9UHD2 (TBK1) , P78527 (PRKDC) , Q9Y2I7 (PIKFYVE) , Q96KB5 (PBK) , Q53ET0 (CRTC2) , Q14164 (IKBKE) , P17252 (PRKCA) , Q5S007 (LRRK2) , P31749 (AKT1) , O15530 (PDPK1) , Q13418 (ILK) , Q15139 (PRKD1) , Q07912 (TNK2) , P42345 (MTOR) , P49137 (MAPKAPK2) , P28482 (MAPK1) , Q13153 (PAK1) | Uniprot |
Y474 | Phosphorylation | Uniprot | |
S475 | Phosphorylation | Uniprot | |
S477 | Phosphorylation | Uniprot | |
T479 | Phosphorylation | Uniprot |
Site | PTM Type | Enzyme | Source |
---|---|---|---|
M1 | Acetylation | Uniprot | |
K14 | Ubiquitination | Uniprot | |
K20 | Ubiquitination | Uniprot | |
K30 | Ubiquitination | Uniprot | |
S34 | Phosphorylation | Uniprot | |
Y38 | Phosphorylation | Uniprot | |
K39 | Ubiquitination | Uniprot | |
T81 | Phosphorylation | Uniprot | |
K111 | Ubiquitination | Uniprot | |
Y122 | Phosphorylation | Uniprot | |
C124 | S-Nitrosylation | Uniprot | |
S126 | Phosphorylation | Uniprot | |
S128 | Phosphorylation | Uniprot | |
S131 | Phosphorylation | Uniprot | |
S141 | Phosphorylation | Uniprot | |
K142 | Ubiquitination | Uniprot | |
K146 | Ubiquitination | Uniprot | |
K156 | Ubiquitination | Uniprot | |
K160 | Ubiquitination | Uniprot | |
Y177 | Phosphorylation | Uniprot | |
Y178 | Phosphorylation | Uniprot | |
K185 | Ubiquitination | Uniprot | |
K191 | Ubiquitination | Uniprot | |
S242 | Phosphorylation | Uniprot | |
K277 | Ubiquitination | Uniprot | |
K285 | Ubiquitination | Uniprot | |
K290 | Ubiquitination | Uniprot | |
K298 | Ubiquitination | Uniprot | |
S302 | Phosphorylation | Uniprot | |
T306 | Phosphorylation | Uniprot | |
T309 | Phosphorylation | Q15118 (PDK1) , O15530 (PDPK1) , P78527 (PRKDC) | Uniprot |
T313 | Phosphorylation | Uniprot | |
Y316 | Phosphorylation | Uniprot | |
Y327 | Phosphorylation | Uniprot | |
K378 | Acetylation | Uniprot | |
K378 | Ubiquitination | Uniprot | |
S379 | Phosphorylation | Uniprot | |
K401 | Ubiquitination | Uniprot | |
K427 | Ubiquitination | Uniprot | |
Y438 | Phosphorylation | Uniprot | |
S447 | Phosphorylation | Uniprot | |
T449 | Phosphorylation | Uniprot | |
T451 | Phosphorylation | Uniprot | |
Y456 | Phosphorylation | Uniprot | |
S458 | Phosphorylation | Uniprot | |
S474 | Phosphorylation | O15530 (PDPK1) , P78527 (PRKDC) | Uniprot |
Y475 | Phosphorylation | Uniprot | |
S476 | Phosphorylation | Uniprot | |
S478 | Phosphorylation | Uniprot |
Site | PTM Type | Enzyme | Source |
---|---|---|---|
S2 | Acetylation | Uniprot | |
K14 | Ubiquitination | Uniprot | |
S34 | Phosphorylation | Uniprot | |
S120 | Phosphorylation | Uniprot | |
S123 | Phosphorylation | Uniprot | |
K156 | Ubiquitination | Uniprot | |
K181 | Ubiquitination | Uniprot | |
S197 | Phosphorylation | Uniprot | |
K273 | Sumoylation | Uniprot | |
K273 | Ubiquitination | Uniprot | |
K281 | Ubiquitination | Uniprot | |
K286 | Ubiquitination | Uniprot | |
T298 | Phosphorylation | Uniprot | |
T302 | Phosphorylation | Uniprot | |
T305 | Phosphorylation | Q15118 (PDK1) , O15530 (PDPK1) , Q05513 (PRKCZ) | Uniprot |
T309 | Phosphorylation | Uniprot | |
Y312 | Phosphorylation | Uniprot | |
Y323 | Phosphorylation | Uniprot | |
T432 | Phosphorylation | Uniprot | |
Y434 | Phosphorylation | Uniprot | |
T440 | Phosphorylation | Uniprot | |
T447 | Phosphorylation | Uniprot | |
S472 | Phosphorylation | Q05513 (PRKCZ) | Uniprot |
Y473 | Phosphorylation | Uniprot | |
S474 | Phosphorylation | Uniprot | |
S476 | Phosphorylation | Uniprot |
翻译修饰 - P31749/P31751/Q9Y243 作为激酶
Substrate | Site | Source |
---|---|---|
O15111 (CHUK) | T23 | Uniprot |
O43464 (HTRA2) | S212 | Uniprot |
O43524 (FOXO3) | T32 | Uniprot |
O43524 (FOXO3) | S253 | Uniprot |
O43524 (FOXO3) | S315 | Uniprot |
O60331 (PIP5K1C) | S555 | Uniprot |
P03372-1 (ESR1) | S167 | Uniprot |
P04406 (GAPDH) | T237 | Uniprot |
P04792 (HSPB1) | S82 | Uniprot |
P15056 (BRAF) | S364 | Uniprot |
P15056 (BRAF) | S428 | Uniprot |
P15056 (BRAF) | T440 | Uniprot |
P15311 (EZR) | T567 | Uniprot |
P16220 (CREB1) | S133 | Uniprot |
P28906 (CD34) | S346 | Uniprot |
P29474 (NOS3) | S615 | Uniprot |
P30405 (PPIF) | S31 | Uniprot |
P35222 (CTNNB1) | S552 | Uniprot |
P46527 (CDKN1B) | T157 | Uniprot |
P49760 (CLK2) | T344 | Uniprot |
P49815 (TSC2) | S939 | Uniprot |
P49815 (TSC2) | T1462 | Uniprot |
P49841 (GSK3B) | S9 | Uniprot |
P55211 (CASP9) | S196 | Uniprot |
P68431 (HIST1H3J) | S11 | Uniprot |
P68431 (HIST1H3J) | S29 | Uniprot |
P68431 (HIST1H3J) | T46 | Uniprot |
P98170 (XIAP) | S87 | Uniprot |
P98177 (FOXO4) | T32 | Uniprot |
Q00987 (MDM2) | S166 | Uniprot |
Q00987 (MDM2) | S186 | Uniprot |
Q01860 (POU5F1) | T235 | Uniprot |
Q09472 (EP300) | S1834 | Uniprot |
Q12778 (FOXO1) | T24 | Uniprot |
Q12778 (FOXO1) | S256 | Uniprot |
Q13043 (STK4) | T387 | Uniprot |
Q13188 (STK3) | T117 | Uniprot |
Q13243 (SRSF5) | S86 | Uniprot |
Q13541 (EIF4EBP1) | T36 | Uniprot |
Q13541 (EIF4EBP1) | T45 | Uniprot |
Q14315 (FLNC) | S2233 | Uniprot |
Q15365 (PCBP1) | S43 | Uniprot |
Q6ZWJ1 (STXBP4) | S99 | Uniprot |
Q7Z6J0 (SH3RF1) | S304 | Uniprot |
Q86YS7 (C2CD5) | S197 | Uniprot |
Q8WX93 (PALLD) | S1118 | Uniprot |
Q92908-2 (GATA6) | S290 | Uniprot |
Q92934 (BAD) | S99 | Uniprot |
Q92934 (BAD) | S118 | Uniprot |
Q92945 (KHSRP) | S193 | Uniprot |
Q96B36 (AKT1S1) | T246 | Uniprot |
Q96F86 (EDC3) | S161 | Uniprot |
Q99683 (MAP3K5) | S83 | Uniprot |
Q99697 (PITX2) | T90 | Uniprot |
Q9GZV1 (ANKRD2) | S99 | Uniprot |
Q9H0H5 (RACGAP1) | T249 | Uniprot |
Q9H0K1 (SIK2) | S358 | Uniprot |
Q9NZJ5 (EIF2AK3) | T802 | Uniprot |
Q9UBK2 (PPARGC1A) | S571 | Uniprot |
Q9Y3M2 (CBY1) | S20 | Uniprot |
Q9Y4I1 (MYO5A) | T1650 | Uniprot |
Substrate | Site | Source |
---|---|---|
O15111 (CHUK) | T23 | Uniprot |
O15119 (TBX3) | S719 | Uniprot |
O43524 (FOXO3) | T32 | Uniprot |
O43524 (FOXO3) | S253 | Uniprot |
O43524 (FOXO3) | S315 | Uniprot |
P04792 (HSPB1) | S82 | Uniprot |
P15056 (BRAF) | S364 | Uniprot |
P15056 (BRAF) | S365 | Uniprot |
P15056 (BRAF) | S428 | Uniprot |
P15056 (BRAF) | S429 | Uniprot |
P16220 (CREB1) | S133 | Uniprot |
P29474 (NOS3) | S615 | Uniprot |
P49841 (GSK3B) | S9 | Uniprot |
P55211 (CASP9) | S196 | Uniprot |
Q01860 (POU5F1) | T235 | Uniprot |
Q13043 (STK4) | T387 | Uniprot |
Q13188 (STK3) | T117 | Uniprot |
Q92934 (BAD) | S99 | Uniprot |
Q92934 (BAD) | S118 | Uniprot |
Q9UKV8 (AGO2) | S387 | Uniprot |
研究背景
AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53. Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility. Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation. Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation.
O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating phosphorylation at Thr-308 via disrupting the interaction between AKT1 and PDPK1. O-GlcNAcylation at Ser-473 also probably interferes with phosphorylation at this site.
Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity. Activated TNK2 phosphorylates it on Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA. This phosphorylated form localizes to the cell membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to its activation. Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation by PDPK1. Phosphorylated at Thr-308 and Ser-473 by IKBKE and TBK1. Ser-473 phosphorylation is enhanced by interaction with AGAP2 isoform 2 (PIKE-A). Ser-473 phosphorylation is enhanced in focal cortical dysplasias with Taylor-type balloon cells. Ser-473 phosphorylation is enhanced by signaling through activated FLT3 (By similarity). Ser-473 is dephosphorylated by PHLPP. Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase. The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase. Ser-473 is dephosphorylated by CPPED1, leading to termination of signaling.
Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome (By similarity). Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation. When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. Also ubiquitinated by TRIM13 leading to its proteasomal degradation. Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation.
Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases EP300 and KAT2B. Acetylation results in reduced phosphorylation and inhibition of activity. Deacetylated at Lys-14 and Lys-20 by SIRT1. SIRT1-mediated deacetylation relieves the inhibition.
Cytoplasm. Nucleus. Cell membrane.
Note: Nucleus after activation by integrin-linked protein kinase 1 (ILK1). Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus. Colocalizes with WDFY2 in intracellular vesicles (PubMed:16792529).
Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Expressed in all human cell types so far analyzed. The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages.
Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). Interacts (via the C-terminus) with CCDC88A (via its C-terminus). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding (By similarity). Interacts with AGAP2 (isoform 2/PIKE-A); the interaction occurs in the presence of guanine nucleotides. Interacts with AKTIP. Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CDKN1B; the interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle progression. Interacts with MAP3K5 and TRAF6. Interacts with BAD, PPP2R5B, STK3 and STK4. Interacts (via PH domain) with SIRT1. Interacts with SRPK2 in a phosphorylation-dependent manner. Interacts with RAF1. Interacts with TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with TNK2 and CLK2. Interacts (via the C-terminus) with THEM4 (via its C-terminus). Interacts with and phosphorylated by PDPK1. Interacts with PA2G4 (By similarity). Interacts with KIF14; the interaction is detected in the plasma membrane upon INS stimulation and promotes AKT1 phosphorylation. Interacts with FAM83B; activates the PI3K/AKT signaling cascade. Interacts with WDFY2 (via WD repeats 1-3). Forms a complex with WDFY2 and FOXO1 (By similarity). Interacts with FAM168A. Interacts with SYAP1 (via phosphorylated form and BSD domain); this interaction is enhanced in a mTORC2-mediated manner in response to epidermal growth factor (EGF) stimulation and activates AKT1. Interacts with PKHM3 (By similarity). Interacts with FKBP5/FKBP51; promoting interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1.
Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction.
The AGC-kinase C-terminal mediates interaction with THEM4.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development.
One of the few specific substrates of AKT2 identified recently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'.
Phosphorylation on Thr-309 and Ser-474 is required for full activity.
Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT2 ubiquitination. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.
O-GlcNAcylation at Thr-306 and Thr-313 inhibits activating phosphorylation at Thr-309 via disrupting the interaction between AKT and PDK1.
Cytoplasm. Nucleus. Cell membrane>Peripheral membrane protein. Early endosome.
Note: Localizes within both nucleus and cytoplasm of proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts. By virtue of the N-terminal PH domain, is recruited to sites of the plasma membrane containing increased PI(3,4,5)P3 or PI(3,4)P2, cell membrane targeting is also facilitared by interaction with CLIP3. Colocalizes with WDFY2 in early endosomes (By similarity).
Expressed in all cell types so far analyzed.
Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CLK2, PBH2 and TRAF6. Interacts (when phosphorylated) with CLIP3, the interaction promotes cell membrane localization. Interacts with WDFY2 (via WD repeats 1-3).
Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.
Phosphorylation on Thr-305 and Ser-472 is required for full activity.
Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.
O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.
Nucleus. Cytoplasm. Membrane>Peripheral membrane protein.
Note: Membrane-associated after cell stimulation leading to its translocation.
In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.
Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6. Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity).
Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
研究领域
· Cellular Processes > Transport and catabolism > Autophagy - animal. (View pathway)
· Cellular Processes > Cell growth and death > Apoptosis. (View pathway)
· Cellular Processes > Cell growth and death > Cellular senescence. (View pathway)
· Cellular Processes > Cellular community - eukaryotes > Focal adhesion. (View pathway)
· Cellular Processes > Cellular community - eukaryotes > Signaling pathways regulating pluripotency of stem cells. (View pathway)
· Environmental Information Processing > Signal transduction > MAPK signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > ErbB signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > Ras signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > Rap1 signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > cGMP-PKG signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > cAMP signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > HIF-1 signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > FoxO signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > Sphingolipid signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > Phospholipase D signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > mTOR signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > AMPK signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > Apelin signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > Jak-STAT signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > TNF signaling pathway. (View pathway)
· Human Diseases > Drug resistance: Antineoplastic > EGFR tyrosine kinase inhibitor resistance.
· Human Diseases > Drug resistance: Antineoplastic > Endocrine resistance.
· Human Diseases > Drug resistance: Antineoplastic > Platinum drug resistance.
· Human Diseases > Endocrine and metabolic diseases > Insulin resistance.
· Human Diseases > Endocrine and metabolic diseases > Non-alcoholic fatty liver disease (NAFLD).
· Human Diseases > Infectious diseases: Parasitic > Chagas disease (American trypanosomiasis).
· Human Diseases > Infectious diseases: Parasitic > Toxoplasmosis.
· Human Diseases > Infectious diseases: Bacterial > Tuberculosis.
· Human Diseases > Infectious diseases: Viral > Hepatitis C.
· Human Diseases > Infectious diseases: Viral > Hepatitis B.
· Human Diseases > Infectious diseases: Viral > Measles.
· Human Diseases > Infectious diseases: Viral > Influenza A.
· Human Diseases > Infectious diseases: Viral > Human papillomavirus infection.
· Human Diseases > Infectious diseases: Viral > HTLV-I infection.
· Human Diseases > Infectious diseases: Viral > Epstein-Barr virus infection.
· Human Diseases > Cancers: Overview > Pathways in cancer. (View pathway)
· Human Diseases > Cancers: Overview > Proteoglycans in cancer.
· Human Diseases > Cancers: Specific types > Colorectal cancer. (View pathway)
· Human Diseases > Cancers: Specific types > Renal cell carcinoma. (View pathway)
· Human Diseases > Cancers: Specific types > Pancreatic cancer. (View pathway)
· Human Diseases > Cancers: Specific types > Endometrial cancer. (View pathway)
· Human Diseases > Cancers: Specific types > Glioma. (View pathway)
· Human Diseases > Cancers: Specific types > Prostate cancer. (View pathway)
· Human Diseases > Cancers: Specific types > Melanoma. (View pathway)
· Human Diseases > Cancers: Specific types > Chronic myeloid leukemia. (View pathway)
· Human Diseases > Cancers: Specific types > Acute myeloid leukemia. (View pathway)
· Human Diseases > Cancers: Specific types > Small cell lung cancer. (View pathway)
· Human Diseases > Cancers: Specific types > Non-small cell lung cancer. (View pathway)
· Human Diseases > Cancers: Specific types > Breast cancer. (View pathway)
· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma. (View pathway)
· Human Diseases > Cancers: Specific types > Gastric cancer. (View pathway)
· Human Diseases > Cancers: Overview > Central carbon metabolism in cancer. (View pathway)
· Human Diseases > Cancers: Overview > Choline metabolism in cancer. (View pathway)
· Organismal Systems > Immune system > Chemokine signaling pathway. (View pathway)
· Organismal Systems > Aging > Longevity regulating pathway. (View pathway)
· Organismal Systems > Aging > Longevity regulating pathway - multiple species. (View pathway)
· Organismal Systems > Circulatory system > Adrenergic signaling in cardiomyocytes. (View pathway)
· Organismal Systems > Development > Osteoclast differentiation. (View pathway)
· Organismal Systems > Immune system > Platelet activation. (View pathway)
· Organismal Systems > Immune system > Toll-like receptor signaling pathway. (View pathway)
· Organismal Systems > Immune system > T cell receptor signaling pathway. (View pathway)
· Organismal Systems > Immune system > B cell receptor signaling pathway. (View pathway)
· Organismal Systems > Immune system > Fc epsilon RI signaling pathway. (View pathway)
· Organismal Systems > Immune system > Fc gamma R-mediated phagocytosis. (View pathway)
· Organismal Systems > Nervous system > Neurotrophin signaling pathway. (View pathway)
· Organismal Systems > Nervous system > Cholinergic synapse.
· Organismal Systems > Nervous system > Dopaminergic synapse.
· Organismal Systems > Endocrine system > Insulin signaling pathway. (View pathway)
· Organismal Systems > Endocrine system > Progesterone-mediated oocyte maturation.
· Organismal Systems > Endocrine system > Estrogen signaling pathway. (View pathway)
· Organismal Systems > Endocrine system > Prolactin signaling pathway. (View pathway)
· Organismal Systems > Endocrine system > Thyroid hormone signaling pathway. (View pathway)
· Organismal Systems > Endocrine system > Adipocytokine signaling pathway.
· Organismal Systems > Endocrine system > Glucagon signaling pathway.
· Organismal Systems > Endocrine system > Regulation of lipolysis in adipocytes.
· Organismal Systems > Endocrine system > Relaxin signaling pathway.
· Organismal Systems > Digestive system > Carbohydrate digestion and absorption.
文献引用
Application: WB Species: mouse Sample: AML cell
Application: WB Species: human Sample: MOLM-13 cells
Application: WB Species: mouse Sample: Liver
Application: IF/ICC Species: mouse Sample: HepG2 cells
Application: WB Species: Mouse Sample:
Application: WB Species: Human Sample: Huh7 and Hep3B cells
Application: WB Species: human Sample: BxPC‐3 and HPAC cells
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