製品: AKT1 Antibody
カタログ: BF0570
タンパク質の説明: Mouse monoclonal antibody to AKT1
アプリケーション: WB ELISA
反応性: Human, Mouse, Monkey
分子量: 56kDa; 56kD(Calculated).
ユニプロット: P31749
RRID: AB_2833758

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製品説明

ソース:
Mouse
アプリケーション:
ELISA 1:10000, WB 1:500-1:2000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human,Mouse,Monkey
クローナリティ:
Monoclonal [AFB1734]
特異性:
AKT1 antibody detects endogenous levels of total AKT1.
RRID:
AB_2833758
引用形式: Affinity Biosciences Cat# BF0570, RRID:AB_2833758.
コンジュゲート:
Unconjugated.
精製:
Affinity-chromatography.
保存:
Mouse IgG1 in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ/展開

AKT 1 antibody;AKT antibody;AKT1 antibody;AKT1_HUMAN antibody;MGC99656 antibody;PKB antibody;PKB-ALPHA antibody;PRKBA antibody;Protein Kinase B Alpha antibody;Protein kinase B antibody;Proto-oncogene c-Akt antibody;RAC Alpha antibody;RAC antibody;RAC-alpha serine/threonine-protein kinase antibody;RAC-PK-alpha antibody;

免疫原

免疫原:

Purified recombinant fragment of human AKT1 expressed in E. Coli.

Uniprot:
遺伝子(ID):
発現特異性:
P31749 AKT1_HUMAN:

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.

タンパク質の説明:
The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Multiple alternatively spliced transcript variants have been found for this gene./AKT2 is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains. Furthermore, AKT2 was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression of AKT2 contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. AKT2 is a general protein kinase capable of phophorylating several known proteins./The protein encoded by this gene is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described.
タンパク質配列:
MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA

PTMs - P31749 基板として

Site PTM Type Enzyme
S2 Phosphorylation
K8 Ubiquitination
K14 Acetylation
K14 Methylation
K14 Ubiquitination
K20 Acetylation
K20 Ubiquitination
K30 Ubiquitination
T34 Phosphorylation O15530 (PDPK1) , Q05513 (PRKCZ)
K39 Ubiquitination
T65 Phosphorylation
T72 Phosphorylation P31749 (AKT1)
T87 Phosphorylation
T92 Phosphorylation
S122 Phosphorylation
S124 Phosphorylation
S126 O-Glycosylation
S126 Phosphorylation
S129 O-Glycosylation
S129 Phosphorylation P68400 (CSNK2A1)
S137 Phosphorylation
K140 Ubiquitination
T146 Phosphorylation
K154 Ubiquitination
K158 Ubiquitination
T172 Phosphorylation
Y176 Phosphorylation Q07912 (TNK2)
K189 Ubiquitination
T211 Phosphorylation
S216 Phosphorylation
C224 S-Nitrosylation
S246 Phosphorylation P31749 (AKT1)
S259 Phosphorylation
K268 Ubiquitination
K276 Sumoylation
K276 Ubiquitination
K284 Ubiquitination
K289 Ubiquitination
T291 Phosphorylation
C296 S-Nitrosylation
K297 Ubiquitination
K301 Sumoylation
K301 Ubiquitination
T305 O-Glycosylation
T305 Phosphorylation
T308 O-Glycosylation
T308 Phosphorylation P31749 (AKT1) , P17252 (PRKCA) , Q9UHD2 (TBK1) , P05771 (PRKCB) , Q15139 (PRKD1) , Q8N5S9 (CAMKK1) , Q14164 (IKBKE) , Q07912 (TNK2) , P78527 (PRKDC) , O15530 (PDPK1)
C310 S-Nitrosylation
T312 O-Glycosylation
T312 Phosphorylation P49840 (GSK3A)
Y315 Phosphorylation Q13882 (PTK6) , P12931 (SRC) , P07949 (RET)
Y326 Phosphorylation P12931 (SRC) , Q13882 (PTK6)
K377 Ubiquitination
S378 Phosphorylation
S396 Phosphorylation
K400 Ubiquitination
Y417 Phosphorylation
K420 Acetylation
K426 Acetylation
K426 Ubiquitination
T435 Phosphorylation
Y437 Phosphorylation
T443 Phosphorylation
T448 Phosphorylation
T450 Phosphorylation P42345 (MTOR)
S457 Phosphorylation
S473 O-Glycosylation
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)
Y474 Phosphorylation
S475 Phosphorylation
S477 Phosphorylation
T479 Phosphorylation

PTMs - P31749 酵素として

Substrate Site Source
O14492 (SH2B2) S598 Uniprot
O14492-2 (SH2B2) S641 Uniprot
O14745 (SLC9A3R1) T156 Uniprot
O14746 (TERT) S227 Uniprot
O14746 (TERT) S824 Uniprot
O14757-1 (CHEK1) S280 Uniprot
O15111 (CHUK) T23 Uniprot
O15151-1 (MDM4) S342 Uniprot
O15151 (MDM4) S367 Uniprot
O15360-1 (FANCA) S1149 Uniprot
O15519 (CFLAR) S273 Uniprot
O43464 (HTRA2) S212 Uniprot
O43521 (BCL2L11) S87 Uniprot
O43524-1 (FOXO3) T32 Uniprot
O43524 (FOXO3) S253 Uniprot
O43524 (FOXO3) S315 Uniprot
O60285 (NUAK1) S600 Uniprot
O60331 (PIP5K1C) S555 Uniprot
O60343 (TBC1D4) S318 Uniprot
O60343 (TBC1D4) S588 Uniprot
O60343 (TBC1D4) T642 Uniprot
O60825 (PFKFB2) S466 Uniprot
O60825 (PFKFB2) S483 Uniprot
O75376 (NCOR1) S1450 Uniprot
O95999 (BCL10) S218 Uniprot
O95999 (BCL10) S231 Uniprot
P00533 (EGFR) S229 Uniprot
P02545 (LMNA) S301 Uniprot
P02545 (LMNA) S404 Uniprot
P03372 (ESR1) S104 Uniprot
P03372 (ESR1) S106 Uniprot
P03372 (ESR1) S118 Uniprot
P03372-1 (ESR1) S167 Uniprot
P03372 (ESR1) S305 Uniprot
P04049-1 (RAF1) S259 Uniprot
P04150 (NR3C1) S134 Uniprot
P04792 (HSPB1) S82 Uniprot
P05106 (ITGB3) T767 Uniprot
P05106 (ITGB3) T779 Uniprot
P05455 (SSB) T302 Uniprot
P07550 (ADRB2) S345 Uniprot
P07550 (ADRB2) S346 Uniprot
P08047 (SP1) S42 Uniprot
P08047 (SP1) T679 Uniprot
P08047 (SP1) S698 Uniprot
P08670 (VIM) S39 Uniprot
P08727 (KRT19) S35 Uniprot
P09601 (HMOX1) S188 Uniprot
P09651 (HNRNPA1) S199 Uniprot
P10275-1 (AR) S208 Uniprot
P10275-1 (AR) S215 Uniprot
P10275-2 (AR) S260 Uniprot
P10275 (AR) S792 Uniprot
P10276 (RARA) S96 Uniprot
P12755 (SKI) T458 Uniprot
P14598 (NCF1) S304 Uniprot
P14598 (NCF1) S328 Uniprot
P15056 (BRAF) S365 Uniprot
P15056 (BRAF) S429 Uniprot
P15976 (GATA1) S310 Uniprot
P16220 (CREB1) S133 Uniprot
P17302 (GJA1) S369 Uniprot
P17302 (GJA1) S373 Uniprot
P17542 (TAL1) T90 Uniprot
P18031 (PTPN1) S50 Uniprot
P19174 (PLCG1) S1248 Uniprot
P19634 (SLC9A1) S648 Uniprot
P19634 (SLC9A1) S703 Uniprot
P19634 (SLC9A1) S796 Uniprot
P21333 (FLNA) S2152 Uniprot
P21453 (S1PR1) T236 Uniprot
P22736 (NR4A1) S351 Uniprot
P23396 (RPS3) T70 Uniprot
P23588 (EIF4B) S422 Uniprot
P23769-1 (GATA2) S401 Uniprot
P24941 (CDK2) T39 Uniprot
P26358 (DNMT1) S143 Uniprot
P26678 (PLN) S16 Uniprot
P29317 (EPHA2) S897 Uniprot
P29401 (TKT) T382 Uniprot
P29401 (TKT) S387 Uniprot
P29474 (NOS3) S615 Uniprot
P29474-1 (NOS3) S1177 Uniprot
P29474 (NOS3) S1179 Uniprot
P30291 (WEE1) S642 Uniprot
P30305 (CDC25B) S353 Uniprot
P31749 (AKT1) T72 Uniprot
P31749 (AKT1) S246 Uniprot
P31749 (AKT1) T308 Uniprot
P31749 (AKT1) S473 Uniprot
P33778 (HIST1H2BB) S37 Uniprot
P35222 (CTNNB1) S552 Uniprot
P35226 (BMI1) S316 Uniprot
P35232 (PHB) T258 Uniprot
P35240 (NF2) S10 Uniprot
P35240 (NF2) T230 Uniprot
P35240 (NF2) S315 Uniprot
P35568 (IRS1) S629 Uniprot
P38398-8 (BRCA1) T462 Uniprot
P38398 (BRCA1) T509 Uniprot
P38398 (BRCA1) S694 Uniprot
P38936 (CDKN1A) T145 Uniprot
P38936 (CDKN1A) S146 Uniprot
P41219 (PRPH) S59 Uniprot
P41279 (MAP3K8) S400 Uniprot
P41279-1 (MAP3K8) S413 Uniprot
P42345 (MTOR) T2446 Uniprot
P42345 (MTOR) S2448 Uniprot
P42858 (HTT) S419 Uniprot
P45985-1 (MAP2K4) S80 Uniprot
P46527 (CDKN1B) S10 Uniprot
P46527 (CDKN1B) T157 Uniprot
P46527 (CDKN1B) T187 Uniprot
P46527 (CDKN1B) T198 Uniprot
P46937 (YAP1) S127 Uniprot
P47870 (GABRB2) S472 Uniprot
P48431 (SOX2) T118 Uniprot
P48730 (CSNK1D) S370 Uniprot
P49760 (CLK2) S34 Uniprot
P49760 (CLK2) T127 Uniprot
P49815 (TSC2) S939 Uniprot
P49815 (TSC2) S981 Uniprot
P49815-1 (TSC2) T1462 Uniprot
P49840 (GSK3A) S21 Uniprot
P49841 (GSK3B) S9 Uniprot
P49918 (CDKN1C) S282 Uniprot
P49918 (CDKN1C) T310 Uniprot
P51617-4 (IRAK1) T66 Uniprot
P51617 (IRAK1) T100 Uniprot
P53365 (ARFIP2) S260 Uniprot
P53804 (TTC3) S378 Uniprot
P54253 (ATXN1) S775 Uniprot
P54274 (TERF1) T273 Uniprot
P54578 (USP14) S432 Uniprot
P54646 (PRKAA2) S491 Uniprot
P55072 (VCP) S352 Uniprot
P55072 (VCP) S746 Uniprot
P55072 (VCP) S748 Uniprot
P55211-1 (CASP9) S183 Uniprot
P55211 (CASP9) S196 Uniprot
P55316 (FOXG1) T279 Uniprot
P56270 (MAZ) T385 Uniprot
P60484-1 (PTEN) S380 Uniprot
P60484-1 (PTEN) S385 Uniprot
P62136 (PPP1CA) T320 Uniprot
P63000 (RAC1) S71 Uniprot
P63104-1 (YWHAZ) S58 Uniprot
P63104-1 (YWHAZ) S184 Uniprot
P67809 (YBX1) S102 Uniprot
P68400 (CSNK2A1) T13 Uniprot
P78362 (SRPK2) T492 Uniprot
P78371 (CCT2) S260 Uniprot
P84022 (SMAD3) T179 Uniprot
P84243 (H3F3B) S11 Uniprot
P98170 (XIAP) S87 Uniprot
P98177 (FOXO4) T32 Uniprot
P98177 (FOXO4) S197 Uniprot
P98177 (FOXO4) S262 Uniprot
P98177-1 (FOXO4) T451 Uniprot
P98177-1 (FOXO4) T455 Uniprot
Q00987 (MDM2) S166 Uniprot
Q00987-11 (MDM2) S172 Uniprot
Q00987 (MDM2) S186 Uniprot
Q00987 (MDM2) S188 Uniprot
Q00987-11 (MDM2) S192 Uniprot
Q01860 (POU5F1) T235 Uniprot
Q04912 (MST1R) S1394 Uniprot
Q05195 (MXD1) S145 Uniprot
Q05397 (PTK2) S695 Uniprot
Q05397 (PTK2) T700 Uniprot
Q06187 (BTK) S51 Uniprot
Q06187 (BTK) T495 Uniprot
Q07352 (ZFP36L1) S92 Uniprot
Q07352 (ZFP36L1) S203 Uniprot
Q07812 (BAX) S184 Uniprot
Q09472 (EP300) S1834 Uniprot
Q12778 (FOXO1) T24 Uniprot
Q12778 (FOXO1) S256 Uniprot
Q12778 (FOXO1) S319 Uniprot
Q12906 (ILF3) S647 Uniprot
Q13009 (TIAM1) S231 Uniprot
Q13043 (STK4) T120 Uniprot
Q13043 (STK4) T387 Uniprot
Q13107 (USP4) S445 Uniprot
Q13131 (PRKAA1) S496 Uniprot
Q13153 (PAK1) S21 Uniprot
Q13188 (STK3) T117 Uniprot
Q13188 (STK3) T384 Uniprot
Q13309 (SKP2) S72 Uniprot
Q13322 (GRB10) S428 Uniprot
Q13370-1 (PDE3B) S295 Uniprot
Q13370-1 (PDE3B) S318 Uniprot
Q13370-1 (PDE3B) S442 Uniprot
Q13541 (EIF4EBP1) T37 Uniprot
Q13541 (EIF4EBP1) T46 Uniprot
Q13541 (EIF4EBP1) S65 Uniprot
Q13950 (RUNX2) S28 Uniprot
Q13950 (RUNX2) S196 Uniprot
Q13950 (RUNX2) T198 Uniprot
Q13950 (RUNX2) T200 Uniprot
Q14315 (FLNC) S2233 Uniprot
Q14457 (BECN1) S295 Uniprot
Q14643 (ITPR1) S2690 Uniprot
Q14957 (GRIN2C) S1081 Uniprot
Q15027 (ACAP1) S554 Uniprot
Q15121 (PEA15) S116 Uniprot
Q15365 (PCBP1) S43 Uniprot
Q15672 (TWIST1) S42 Uniprot
Q15672 (TWIST1) S123 Uniprot
Q15910-2 (EZH2) S21 Uniprot
Q15942 (ZYX) S142 Uniprot
Q16584 (MAP3K11) S674 Uniprot
Q16763 (UBE2S) T152 Uniprot
Q16875 (PFKFB3) S461 Uniprot
Q3V6T2-2 (CCDC88A) S1417 Uniprot
Q53EL6 (PDCD4) S67 Uniprot
Q53EL6 (PDCD4) S457 Uniprot
Q5VWQ8 (DAB2IP) S971 Uniprot
Q6R327 (RICTOR) T1135 Uniprot
Q7L5N1 (COPS6) S60 Uniprot
Q7Z589 (EMSY) S209 Uniprot
Q7Z5H3 (ARHGAP22) S16 Uniprot
Q7Z6J0 (SH3RF1) S304 Uniprot
Q86TI0 (TBC1D1) S235 Uniprot
Q86TI0 (TBC1D1) T596 Uniprot
Q86V81 (ALYREF) S34 Uniprot
Q86V81 (ALYREF) T219 Uniprot
Q86VP3 (PACS2) S437 Uniprot
Q86YN6 (PPARGC1B) S570 Uniprot
Q8IYJ3 (SYTL1) S241 Uniprot
Q8N6T7 (SIRT6) S338 Uniprot
Q8NCD3 (HJURP) S486 Uniprot
Q8WX93 (PALLD) S1118 Uniprot
Q8WYL5 (SSH1) T826 Uniprot
Q92547 (TOPBP1) S1159 Uniprot
Q92793 (CREBBP) T1871 Uniprot
Q92794 (KAT6A) T369 Uniprot
Q92879 (CELF1) S28 Uniprot
Q92934 (BAD) S75 Uniprot
Q92934 (BAD) S99 Uniprot
Q92934 (BAD) S118 Uniprot
Q92945 (KHSRP) S193 Uniprot
Q96B36 (AKT1S1) T246 Uniprot
Q96F86 (EDC3) S161 Uniprot
Q96HP0 (DOCK6) S1194 Uniprot
Q96QB1-1 (DLC1) S327 Uniprot
Q96QB1-1 (DLC1) S329 Uniprot
Q96QB1-1 (DLC1) S567 Uniprot
Q96QB1-2 (DLC1) S764 Uniprot
Q96QB1-2 (DLC1) S766 Uniprot
Q96QB1-2 (DLC1) S1004 Uniprot
Q96S44 (TP53RK) S250 Uniprot
Q99418 (CYTH2) T276 Uniprot
Q99490-2 (AGAP2) S472 Uniprot
Q99490-2 (AGAP2) S629 Uniprot
Q99490 (AGAP2) S985 Uniprot
Q99502 (EYA1) S299 Uniprot
Q99623 (PHB2) S91 Uniprot
Q99640 (PKMYT1) S83 Uniprot
Q99683 (MAP3K5) S83 Uniprot
Q99697 (PITX2) T90 Uniprot
Q9BPZ7 (MAPKAP1) T86 Uniprot
Q9BRQ0 (PYGO2) S48 Uniprot
Q9BVI0 (PHF20) S265 Uniprot
Q9BVI0 (PHF20) S291 Uniprot
Q9BWT1 (CDCA7) T163 Uniprot
Q9BZQ8 (FAM129A) S602 Uniprot
Q9GZV1 (ANKRD2) S99 Uniprot
Q9H3Z4 (DNAJC5) S10 Uniprot
Q9H4A3 (WNK1) T60 Uniprot
Q9H4X1-2 (RGCC) S45 Uniprot
Q9H6Z4 (RANBP3) S126 Uniprot
Q9H9Q4 (NHEJ1) T181 Uniprot
Q9HBH7 (BEX1) S102 Uniprot
Q9NR28 (DIABLO) S67 Uniprot
Q9NWV8 (BABAM1) S29 Uniprot
Q9NZJ5 (EIF2AK3) T802 Uniprot
Q9P0V3 (SH3BP4) S246 Uniprot
Q9UBK2 (PPARGC1A) S571 Uniprot
Q9UBP6 (METTL1) S27 Uniprot
Q9UKV3 (ACIN1) S1180 Uniprot
Q9UKV3 (ACIN1) S1329 Uniprot
Q9UN36 (NDRG2) S332 Uniprot
Q9UN36 (NDRG2) T348 Uniprot
Q9UQB3 (CTNND2) T457 Uniprot
Q9UQC2 (GAB2) S159 Uniprot
Q9Y261 (FOXA2) T156 Uniprot
Q9Y2I7 (PIKFYVE) S307 Uniprot
Q9Y2I7 (PIKFYVE) S318 Uniprot
Q9Y2V2 (CARHSP1) S52 Uniprot
Q9Y3C5 (RNF11) T135 Uniprot
Q9Y3M2 (CBY1) S20 Uniprot

研究背景

機能:

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.

PTMs:

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.

細胞の位置付け:

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).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

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.

サブユニット構造:

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.

タンパク質ファミリー:

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.

研究領域

· 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.

参考文献

1). The co‑treatment of metformin with flavone synergistically induces apoptosis through inhibition of PI3K/AKT pathway in breast cancer cells. Oncology Letters, 2018 (PubMed: 29552226) [IF=2.9]

Application: WB    Species: human    Sample: breast cancer

Figure 2. |The combination of metformin and flavone synergistically inhibited the PI3K/AKT pathway in breast cancer cells. (A) Protein levels for PI3K , AKT and p‑AKT(ser‑473) were detected with western blotting when MDA‑MB‑231 cells (left column) were treated with 0, 20 mM MET, 100 µM FLA and the combination of 20 mM MET:100 µM FLA for 24 h, and MCF‑7 cells (right column) were the same treatment to test PI3K, AKT and p‑AKT(ser‑473) expressions

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