RHEB2, MEK1(MAP2K1), PtdIns(4,5)P2, Caspase-3, PDK (PDPK1), 18.104.22.168, ERK1/2, c-Jun, IGF-1, mTOR, PCNA, MEK2(MAP2K2), FOXO3A, p53, p21, FAK1, p130CAS, c-Cbl, Shc, GSK3 beta, BAD, Paxillin, EGF, PI3K reg class IA, H-Ras, MAGI-2, SOS, PTEN, c-Src, Tcf(Lef), alpha-5/beta-1 integrin, IRS-1, PI3K cat class IA, Beta-catenin, MAGI-3, EGFR, PtdIns(3,4,5)P3, IGF-1 receptor, Tuberin, ILK, GRB2, 22.214.171.124, AKT(PKB), c-Raf-1, MDM2, Caspase-9
Phosphatase and tensin homolog ( PTEN ) is a known tumor suppressor. It inhibits growth factor-induced cell proliferation, division and regulates Integrin -mediated cell adhesion and survival .
PTEN antagonizes Phosphoinositide-3-kinase ( PI3K ), dephosphorylating Phosphatidylinositol (3,4,5) ( PtdIns(3,4,5)P3 ) and inhibits V-akt murine thymoma viral oncogene homolog 1 ( PI3K )/ AKT -mediated signaling pathways .As a result, PTEN prevents Insulin-like growth factor 1 ( IGF-1 ) signaling ,  and activation of the Epidermal growth factor receptor ( EGFR )-induced FK506 binding protein 12-rapamycin associated protein 1 ( mTOR ) . PTEN also inhibits Mdm2 p53 binding protein homolog ( MDM2 ) and protects Tumor protein p53 ( p53 ) via PI3K/ AKT -dependent as well as via direct binding of p53 thus blocking antiapoptotic processes , . Prevention of PI3K/ AKT pathway activation by PTEN also increases activity of Glycogen synthase kinase 3 ( GSK3 ). This leads to decrease of Beta-catenin nuclear accumulation and prevents transcription of the Transcription factor 7 (in a complex Tcf(Lef) ) and others genes. Thus, PTEN antagonizes Integrin/Integrin-linked kinase ( ILK )-mediated nuclear accumulation of Beta-catenin . Inhibition of PI3K/ AKT decreases Cyclin-dependent kinase inhibitor 1A ( p21 )-mediated cell cycle regulation . PTEN -dependent PI3K/AKT inhibition also decreases Caspase 9 apoptosis-related cysteine peptidase ( Caspase-9 ) activity , as well as the apoptosis mediated by Forkhead box O3 ( FOXO3A )-mediated  and BCL2-associated agonist of cell death ( BAD ) .
PTEN dephosphorylates PTK2 protein tyrosine kinase 2 ( FAK1 ) and SHC transforming protein 1 ( Shc ). This prevents Integrin (for example alpha-5/beta-1 integrin )/ FAK1 and Shc/ Growth factor receptor-bound protein 2 ( GRB2 ) ,  and EGF/ Shc/ GRB2 -mediated  Mitogen-activated protein kinase 1/3 ( ERK1/2 ) activation. ERK1/2 inhibition prevents cell spreading, migration ,  and growth. Dephosphorylation of FAK1 also disrupts its binding of Paxillin and Breast cancer anti-estrogen resistance 1 ( p130CAS ) .
PTEN binds Membrane associated guanylate kinase WW and PDZ domain containing ( MAGI ) proteins. This enhances the efficiency of PTEN signaling through the formation of the PTEN/ MAGI complexes . Caspase 3 apoptosis-related cysteine peptidase ( Caspase-3 ) cleaves PTEN. This inhibits the PTEN pathway .