Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Signal transduction PTEN pathway


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Signal transduction PTEN pathway

PTEN pathway

Phosphatase and tensin homolog ( PTEN ) is a known tumor suppressor. Itinhibits growth factor-induced cell proliferation, division and regulates Integrin-mediated cell adhesion and survival [1].

PTEN antagonizes Phosphoinositide-3-kinase ( PI3K ), dephosphorylatingPhosphatidylinositol (3,4,5) ( PtdIns(3,4,5)P3 ) and inhibits V-akt murine thymomaviral oncogene homolog 1 ( PI3K )/ AKT -mediated signaling pathways [1].As a result, PTEN prevents Insulin-like growth factor 1 ( IGF-1 )signaling [2], [3] and activation of the Epidermal growthfactor receptor ( EGFR )-induced FK506 binding protein 12-rapamycin associatedprotein 1 ( mTOR ) [4]. PTEN also inhibits Mdm2 p53 bindingprotein homolog ( MDM2 ) and protects Tumor protein p53 ( p53 ) viaPI3K/ AKT -dependent as well as via direct binding of p53 thusblocking antiapoptotic processes [5],[6]. Prevention ofPI3K/ AKT pathway activation by PTEN also increases activity ofGlycogen synthase kinase 3 ( GSK3 ). This leads to decrease of Beta-cateninnuclear accumulation and prevents transcription of the Transcription factor 7 (in acomplex Tcf(Lef) ) and others genes. Thus, PTEN antagonizesIntegrin/Integrin-linked kinase ( ILK )-mediated nuclear accumulation ofBeta-catenin [7]. Inhibition of PI3K/ AKT decreasesCyclin-dependent kinase inhibitor 1A ( p21 )-mediated cell cycle regulation [8]. PTEN -dependent PI3K/AKT inhibition also decreases Caspase 9apoptosis-related cysteine peptidase ( Caspase-9 ) activity [9], aswell as the apoptosis mediated by Forkhead box O3 ( FOXO3A )-mediated [10] and BCL2-associated agonist of cell death ( BAD ) [11].

PTEN dephosphorylates PTK2 protein tyrosine kinase 2 ( FAK1 ) and SHCtransforming protein 1 ( Shc ). This prevents Integrin (for examplealpha-5/beta-1 integrin )/ FAK1 and Shc/ Growth factorreceptor-bound protein 2 ( GRB2 ) [12], [13] and EGF/ Shc/ GRB2 -mediated [12] Mitogen-activated protein kinase 1/3( ERK1/2 ) activation. ERK1/2 inhibition prevents cell spreading, migration[12], [13] and growth. Dephosphorylation of FAK1 alsodisrupts its binding of Paxillin and Breast cancer anti-estrogen resistance 1 (p130CAS ) [14].

PTEN binds Membrane associated guanylate kinase WW and PDZ domain containing (MAGI ) proteins. This enhances the efficiency of PTEN signaling through theformation of the PTEN/ MAGI complexes [15]. Caspase 3apoptosis-related cysteine peptidase ( Caspase-3 ) cleaves PTEN. Thisinhibits the PTEN pathway [16].