mutated in multiple advanced cancers 1; protein tyrosine phosphatase PTEN; phosphatase & tensin homolog deleted on chromosome ten; phosphatase & tensin homolog; phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase & dual-specificity protein phosphatase PTEN (PTEN, MMAC1, TEP1)

^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]

Function

tumor suppressor
acts as a dual-specificity protein phosphatase, dephosphorylating Tyr-, Ser- & Thr-phosphorylated proteins
also acts as a lipid phosphatase, removing phosphate in the D3 position of the inositol ring from
- phosphatidylinositol 3,4,5-trisphosphate
- phosphatidylinositol 3,4-phosphate
- phosphatidylinositol 3-phosphate
- inositol 1,3,4,5-tetrakisphosphate
order of substrate preference in vitro: Ptdins(3,4,5)P3 > Ptdins(3,4)P2 > Ptdins3P > ins(1,3,4,5)P4
lipid phosphatase activity is critical for its tumor suppressor function
antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides thus modulating cell cycle progression & cell survival
unphosphorylated form cooperates with AIP1 to suppress AKT1 activation
dephosphorylates Tyr-phosphorylated focal adhesion kinase & inhibits:
- cell migration
- integrin-mediated cell spreading
- focal adhesion formation
may be a negative regulator of insulin signaling & glucose metabolism in adipose tissue
phosphorylation results in an inhibited activity towards PIP3
phosphorylation can both inhibit & promote PDZ-binding
unphosphorylated form interacts with 2nd PDZ domain of AIP1 & with DLG1 & MAST2 in vitro
interacts with MAGI3
in mouse brain tumor model, PTEN reconstitution
- diminished phosphorylation of protein kinase B/Akt
- induced thrombospondin 1 expression
- suppressed angiogenic activity^[3].

phosphatidylinositol 3,4,5-triphosphate +H2O
                  <-->
phosphatidylinositol 4,5-bisphosphate + phosphate

phosphoprotein + H2O <--> a protein + phosphate

protein tyrosine phosphate + H2O <--> protein tyrosine + phosphate

Cofactor: Mg+2

monomer
the C2 domain binds phospholipid membranes in vitro (Ca+2-independent); Ca+2 binding is important for its tumor suppressor function
contains 1 C2 tensin-type domain
contains 1 phosphatase tensin-type domain

expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney & pancreas
expression induced by p53^[4]
expression is down-regulated by TGF-beta

↑ Steck PA et al, Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997 Apr;15(4):356-62. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9090379
↑ Li J et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer Science 275(5308):1943 1997 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9072974s
↑ ^3.0 ^3.1 Wen S et al. PTEN controls tumor-induced angiogenesis. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4622-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11274365
↑ ^4.0 ^4.1 Stambolic V et al. Regulation of PTEN transcription by p53. Molecular Cell 8:317-325 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11545734
↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5728
↑ UniProt http://www.uniprot.org/uniprot/P60484.html
↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/PTENID158.html
↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=PTEN