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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 - AKT

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...   更多...

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

AMPA受体

GRIA1 (Glutamate Receptor, Ionotropic, AMPA 1):

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their...   更多...

GRIA2 (Glutamate Receptor, Ionotropic, AMPA 2):

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. These channels are assembled...   更多...

细胞凋亡

BCL2 (B-Cell CLL/lymphoma 2):

This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends. [provided by...   更多...

MDM2 (Mdm2, p53 E3 Ubiquitin Protein Ligase Homolog (Mouse)):

This gene is a target gene of the transcription factor tumor protein p53. The encoded protein is a nuclear phosphoprotein that binds and inhibits transactivation by tumor protein p53, as part of an autoregulatory negative feedback loop. Overexpression of this gene can result in excessive inactivation of tumor protein p53, diminishing its tumor suppressor function. This protein has E3 ubiquitin...   更多...

细胞周期

CCNA2 - Cyclin A

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. In contrast to cyclin A1,...   更多...

CDKN1A (Cyclin-Dependent Kinase Inhibitor 1A (p21, Cip1)):

This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in...   更多...

细胞成活

EIF4EBP1 (Eukaryotic Translation Initiation Factor 4E Binding Protein 1):

This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is...   更多...

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

This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation...   更多...

葡萄糖代

GYS1 - Glycogen Synthase 1

The protein encoded by this gene catalyzes the addition of glucose monomers to the growing glycogen molecule through the formation of alpha-1,4-glycoside linkages. Mutations in this gene are associated with muscle glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009].   更多...

PIP5K1B (Phosphatidylinositol-4-Phosphate 5-Kinase, Type I, beta):

Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. Mediates RAC1-dependent reorganization of actin filaments. Contributes to the activation of PLD2. Together with PIP5K1A is required after stimulation of G-protein coupled receptors for stable platelet adhesion (By similarity).   更多...

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

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

免疫反应

GSK3a - GSK3 alpha

This gene encodes a multifunctional Ser/Thr protein kinase that is implicated in the control of several regulatory proteins including glycogen synthase, and transcription factors, such as JUN. It also plays a role in the WNT and PI3K signaling pathways, as well as regulates the production of beta-amyloid peptides associated with Alzheimer's disease. [provided by RefSeq, Oct 2011].   更多...

NCF1 (Neutrophil Cytosol Factor 1):

The protein encoded by this gene is a 47 kDa cytosolic subunit of neutrophil NADPH oxidase. This oxidase is a multicomponent enzyme that is activated to produce superoxide anion. Mutations in this gene have been associated with chronic granulomatous disease. [provided by RefSeq, Jul 2008].   更多...

mTORC1

MLST8 (mTOR Associated Protein, LST8 Homolog (S. Cerevisiae)):

RPTOR - Raptor

This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and...   更多...

mTORC2

DEPTOR (DEP Domain Containing mTOR-Interacting Protein):

Negative regulator of the mTORC1 and mTORC2 signaling pathways. Inhibits the kinase activity of both complexes (By similarity).   更多...

TNPO1 - Transportin 1

This gene encodes the beta subunit of the karyopherin receptor complex which interacts with nuclear localization signals to target nuclear proteins to the nucleus. The karyopherin receptor complex is a heterodimer of an alpha subunit which recognizes the nuclear localization signal and a beta subunit which docks the complex at nucleoporins. Alternate splicing of this gene results in two...   更多...

神经发育

HTT - Huntingtin

Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range in the number of trinucleotide repeats has been identified in normal...   更多...

原代狗肾(细胞)

PDPK1 (3-phosphoinositide Dependent Protein Kinase-1):

Serine/threonine kinase required for embryonic development. Inhibits apoptosis. Acts in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and activating Akt1 and S6k. May be involved in axonal pathfinding and synaptogenesis, and in spermatogenesis.   更多...

PDK1 (Pyruvate Dehydrogenase Kinase, Isozyme 1):

Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK)...   更多...

PDK3 (Pyruvate Dehydrogenase Kinase, Isozyme 3):

PHLPP

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

This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by...   更多...

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

PI3K

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

Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. [provided by RefSeq, Jul 2008].   更多...

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

Phosphatidylinositol 3-kinases (PI3Ks) phosphorylate the inositol ring of phosphatidylinositol at the 3-prime position, and play important roles in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PI3Ks are divided into three classes: I, II and III, and only the class I PI3Ks are involved in oncogenesis. This gene encodes the 101 kD regulatory...   更多...

PIK3CG (Phosphoinositide-3-Kinase, Catalytic, gamma Polypeptide):

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

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

PP2A

PPP2CA - Protein Phosphatase 2, Catalytic Subunit, alpha Isozyme

This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes...   更多...

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

Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55,...   更多...

MTS - Microtubule Star:

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):

PPP2R5D (Protein Phosphatase 2, Regulatory Subunit B', delta):

PPP2R5E (Protein Phosphatase 2, Regulatory Subunit B', epsilon Isoform):

PPP2CA - 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):

This gene encodes a protein that specifically complexes with the C-terminus of hepatitis B virus X protein (HBx). The function of this protein is to negatively regulate HBx activity and thus to alter the replication life cycle of the virus. [provided by RefSeq, Jul 2008].   更多...

LAMTOR2 (Late Endosomal/lysosomal Adaptor, MAPK and mTOR Activator 2):

The product of this gene is highly conserved with a mouse protein associated with the cytoplasmic face of late endosomes and lysosomes. The mouse protein interacts with MAPK scaffold protein 1, a component of the mitogen-activated protein kinase pathway. In humans, a mutation in this gene has been associated with a primary immunodeficiency syndrome, and suggests a role for this protein in...   更多...

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

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

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