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PI3K-Akt Signaling

PI3K/Akt通路在细胞稳态、神经发育、新陈代谢及其他过程中均发挥着关键作用。它调节着细胞发育的各个方面,如细胞凋亡、细胞周期进程和细胞分化。

PI3K/Akt通路的关键调节因子为Akt/PKB——一个由三种紧密相关的丝氨酸/苏氨酸-蛋白激酶组成的家族。其中Akt1/PKBα在细胞增殖和细胞代谢中扮演着重要角色。Akt2/PKBβ对葡萄糖代谢具有十分重要的意义。而Akt3/PKBγ则是Akt家族中特征最不明显的成员,但是它主要在脑中表达,被认为主要负责调节线粒体的生物合成。

Akt突变常常会导致对这些过程的调节能力降低以及出现各种形式的癌症。Akt的过度活化还会导致醣酵解增强,从而为癌细胞的代谢转化提供支持。据研究发现,Akt与肿瘤耐药性的发展存在关联,因此它也成了临床前和临床研究的对象。然而,仅仅Akt激活本身并不足以产生癌症表型,这往往还需要其他突变参与其中。

Akt主要调节因子PI3K和PTEN的功能丧失可导致Akt过度活化。作为一个酶家族,PI3Ks可磷酸化PtdIns (Phosphatidylinositol,磷脂酰肌醇),生成3,4,5-三磷酸磷脂酰肌醇(PIP3)。当被受体酪氨酸激酶激活时,PI3K将PIP2磷酸化为PIP3,而后者随后可激活Akt信号传导。而通过将PIP3去磷酸化为PIP2,PTEN则充当着信号转导的负调控因子。

Akt

AKT1 (V-Akt Murine Thymoma Viral Oncogene Homolog 1):

AKT2 (V-Akt Murine Thymoma Viral Oncogene Homolog 2):

AKT3 (V-Akt Murine Thymoma Viral Oncogene Homolog 3 (Protein Kinase B, Gamma)):

AMPA受体

细胞凋亡

细胞周期

细胞成活

RPS6KB1 (Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1):

ATG13 (Autophagy Related 13):

RPS6KB2 (Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 2):

葡萄糖代

PFKFB2 (6-phosphofructo-2-Kinase/fructose-2,6-Biphosphatase 2):

PIP5K1A (Phosphatidylinositol-4-Phosphate 5-Kinase, Type I, alpha):

PIP5K1C (Phosphatidylinositol-4-Phosphate 5-Kinase, Type I, gamma):

免疫反应

mTORC1

mTORC2

DEPTOR (DEP Domain Containing mTOR-Interacting Protein):

MAPKAP1 (Mitogen-Activated Protein Kinase Associated Protein 1):

GBL (G protein beta subunit-like):

PRR5 (Proline Rich 5 (Renal)):

神经发育

原代狗肾(细胞)

PDK1 (Pyruvate Dehydrogenase Kinase 1):

PDK2 (Pyruvate Dehydrogenase Kinase, Isozyme 2):

PDK3 (Pyruvate Dehydrogenase Kinase, Isozyme 3):

PDK4 (Pyruvate Dehydrogenase Kinase, Isozyme 4):

PHLPP

PHLPP1 (PH Domain and Leucine Rich Repeat Protein Phosphatase 1):

PHLPP2 (PH Domain and Leucine Rich Repeat Protein Phosphatase 2):

PI3K

PIK3CA (Phosphoinositide-3-Kinase, Catalytic, alpha Polypeptide):

PIK3R5 (Phosphoinositide-3-Kinase, Regulatory Subunit 5):

PIK3R6 (Phosphoinositide-3-Kinase, Regulatory Subunit 6):

PIK3R5 (Phosphoinositide-3-Kinase, Regulatory Subunit 5):

PP2A

PPP2CA (Protein Phosphatase 2, Catalytic Subunit, alpha Isozyme):

PPP2R4 (Protein Phosphatase 2A Activator, Regulatory Subunit 4):

MTS - Microtubule Star:

PPP2R1A (Protein Phosphatase 2, Regulatory Subunit A, alpha):

PPP2R1B (Protein Phosphatase 2, Regulatory Subunit A, beta):

PPP2R3A (Protein Phosphatase 2, Regulatory Subunit B'', alpha):

PPP2R3C (Protein Phosphatase 2, Regulatory Subunit B'', gamma):

PPP2R5A (Protein Phosphatase 2, Regulatory Subunit B', alpha):

PPP2R5B (Protein Phosphatase 2, Regulatory Subunit B', beta):

PPP2R5C (Protein Phosphatase 2, Regulatory Subunit B', gamma):

PPP2R2B (Protein Phosphatase 2, Regulatory Subunit B, beta):

PPP2R2C (Protein Phosphatase 2, Regulatory Subunit B, gamma):

PPP2R3B (Protein Phosphatase 2A 48 KDa Regulatory Subunit):

其他

HBXIP (Hepatitis B Virus X-Interacting Protein):

MAPKSP1 (Mitogen-Activated Protein Kinase Kinase 1 Interacting Protein 1):

PITRM1 (Pitrilysin Metallopeptidase 1):

PPP1R2 (Protein Phosphatase 1, Regulatory (Inhibitor) Subunit 2):

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