Reactome | PREX2 binds PTEN and inhibits it

PREX2 binds PTEN and inhibits it

Stable Identifier

R-HSA-8850961

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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PREX2, a RAC1 guanine nucleotide exchange factor (GEF), binds to PTEN and inhibits its catalytic activity, resulting in enhanced PI3K/AKT signaling (Fine et al. 2009). The interaction involves the inositol polyphosphate 4-phosphatase domain and the pleckstrin homology (PH) domain of PREX2 and the PDZ binding domain, the phosphatase domain and the C2 domain of PTEN (Fine et al. 2009, Hodakoski et al. 2014). PREX2 binds both the unphosphorylated PTEN and PTEN phosphorylated at the C-terminal tail by casein kinase II, but inhibits the lipid phosphatase activity of phosphorylated PTEN only (Hodakoski et al. 2014). The GEF activity of PREX2 is not needed for PTEN inhibition (Fine et al. 2009).

PREX2 is frequently overexpressed in breast and prostate cancer (Fine et al. 2009) and mutated in melanoma (Berger et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
24367090	Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis Kern, PA, Keniry, M, Anderson, KE, Hawkins, PT, Mense, SM, Barrows, D, Stephens, LR, Parsons, R, Hodakoski, C, Hopkins, BD	Proc. Natl. Acad. Sci. U.S.A.	2014
19729658	Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a Keniry, M, Koujak, S, Hibshoosh, H, Sulis, ML, Fine, B, Mense, S, Maurer, M, Saal, LH, Su, T, Parsons, R, Hodakoski, C, Hopkins, B	Science	2009