本公司经销phospho-AKT1/2/3 （Tyr315/316/312），磷酸化蛋白激酶AKT1,2,3抗体，克隆类型为polyclonal，宿主来源是Rabbit，phospho-AKT1/2/3 （Tyr315/316/312）磷酸化蛋白激酶AKT1,2,3抗体可应用于WB、elisa、IP、IF、IHC等实验，欢迎垂询订购！

货号：BY-5193R
英文名称：Anti-phospho-AKT1/2/3 （Tyr315/316/312）
中文名称：磷酸化蛋白激酶AKT1,2,3抗体
其他名称：phospho-AKT1/AKT2/AKT3 （Tyr315+Tyr316+Tyr312）; AKT1/AKT2/AKT3（phospho-Tyr315/316/312）; AKT 1; AKT; AKT1; AKT-1; AKT1_HUMAN; AKT 2; AKT2; AKT-2; AKT2_HUMAN; AKT 3; AKT3; AKT-3; AKT3_HUMAN; C AKT; cAKT; MGC9965; MGC99656; Oncogene AKT1; PKB; PKB alpha; PKB-ALPHA; PKB beta; PKB gamma; PRKBA; Protein Kinase B Alpha; Protein kinase B; Proto-oncogene c-Akt; RAC Alpha; RAC alpha serine/threonine protein kinase; RAC; RAC PK Alpha; Rac protein kinase alpha; RAC Serine/Threonine Protein Kinase; RAC-alpha serine/threonine-protein kinase; RAC-PK-alpha; v akt murine thymoma viral oncogene homolog 1; vAKT Murine Thymoma Viral Oncogene Homolog 1.
抗体来源：Rabbit
克隆类型：polyclonal
蛋白分子量：predicted molecular weight: 56kDa
纯化方法：affinity purified by Protein A
交叉反应：hu, mo, rat, shp, pig, dog, chk, cow, Rb
产品介绍：AKT, also known as protein kinase B （PKB）, is a 57 kDa serine/threonine protein kinase. There are three mammalian isoforms of Akt: AKT1 （PKB alpha）, AKT2 （PKB beta） ａnd AKT3 （PKB gamma） with AKT2 ａnd AKT3 being approximately 82% identical with the AKT1 isoform. Each isoform has a pleckstrin homology （PH）domain, a kinase domain ａnd a carboxy terminal regulatory domain. AKT was originally cloned from the retrovirus AKT8, ａnd is a key regulator of many signal transduction pathways. Its tight control over cell proliferation ａnd cell viability are manifold; overexpression or inappropriate activation of AKT has been seen in many types of cancer. AKT mediates many of the downstream events of phosphatidylinositol 3 kinase （a lipid kinase activated by growth factors, cytokines ａnd insulin）. PI3 kinase recruits AKT to the membrane, where it is activated by PDK1 phosphorylation. Once phosphorylated, AKT dissociates from the membrane ａnd phosphorylates targets in the cytoplasm ａnd the cell nucleus.Function : 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. 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. 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.AKT1-specific substrates have been recently identified, including palladin （PALLD）, which phosphorylation modulates cytoskeletal organization ａnd cell motility; prohibitin （PHB）, playing an important role in cell metabolism ａnd proliferation; ａnd 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.Subunit : Interacts （via the C-terminus） with CCDC88A （via its C-terminus）. Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding. 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.Subcellular Location : Cytoplasm. Nucleus. Cell membrane （By similarity）. Note=Nucleus after activation by integrin-linked protein kinase 1 （ILK1） （By similarity）. 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.Tissue Specificity : 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.Post-translational modifications : 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. 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. Dephosphorylated at Thr-308 ａnd Ser-473 by PP2A phosphatase. The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase.Ubiquitinated via ＇Lys-48＇-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome. 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.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.DISEASE : Defects in AKT1 are a cause of susceptibility to breast cancer （BC） [MIM:114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically ａnd genetically heterogeneous. Important genetic factors have been indicated by familial occurrence ａnd bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Defects in AKT1 are associated with colorectal cancer （CRC） [MIM:114500]. Note=Genetic variations in AKT1 may play a role in susceptibility to ovarian cancer. Defects in AKT1 are a cause of Proteus syndrome （PROTEUSS） [MIM:176920]. A highly variable, severe disorder of asymmetric ａnd disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, ａnd vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes.Similarity : Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.Contains 1 AGC-kinase C-terminal domain.Contains 1 PH domain.Contains 1 protein kinase domain.Database links : UniProtKB/Swiss-Prot: P31749.2