PH domain leucine-rich repeat-containing protein phosphatase 2; PH domain leucine-rich repeat-containing protein phosphatase-like; PHLPP-like (PHLPP2, KIAA0931, PHLPPL)
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Function
- protein phosphatase
- mediates dephosphorylation of Ser-473 of AKT1, Ser-660 of PRKCB isoform beta-2 & Ser-657 of PRKCA
- AKT1 regulates the balance between cell survival & apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro-apoptotic & anti-apoptotic genes.
- dephosphorylation of Ser-473 of AKT1 triggers apoptosis & decreases cell proliferation
- also controls phosphorylation of AKT3
- dephosphorylation of PRKCA & PRKCB leads to their destabilization & degradation
- inhibits cancer cell proliferation
- may act as a tumor suppressor
- interacts with AKT1, AKT3 & PRKCB isoform beta-2
Cofactor: binds 2 Mn+2 per subunit (putative)
Structure
- contains 22 LRR repeats (leucine-rich repeats)
- contains 1 PH domain
- contains 1 PP2C-like domain
Compartment
- cytoplasm, membrane
- in colorectal cancer tissue, expression is concentrated in cytoplasm & nucleus
Alternative splicing
named isoforms=3
Expression
- in colorectal cancer tissue, expression is highest in the surface epithelium of normal colonic mucosa adjacent to the cancer tissue but is largely excluded from the crypt bases
Pathology
- expression is lost or significantly decreased in 80% of tested tumors (at protein level)