Inositol polyphosphate 5-phosphatases or
phosphoinositide 5-phosphatases (PI 5-phosphatases) are
enzymes that can act on soluble
inositol phosphates and/or
phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human
genetic diseases, in particular the Lowe
protein or OCRL which is mutated in the
Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates,
PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific
proteins to signaling complexes.
Protein kinase B is one target
protein and activation of the
kinase will have a major impact on cell proliferation, survival and cell metabolism. Two other PIs, PI(4,5)P2 and
PI(3,4)P2, are produced or used as substrates of PI 5-phosphatases (OCRL, INPP5B, SHIP1/2, SYNJ1/2, INPP5K, INPP5J, INPP5E). The
inositol lipids may influence many aspects of cytoskeletal organization, lamellipodia formation and
F-actin polymerization. PI 5-phosphatases have been reported to control cell migration, adhesion, polarity and cell invasion particularly in
cancer cells. In
glioblastoma, reducing SHIP2 expression can positively or negatively affect the speed of cell migration depending on the
glioblastoma cell type. The two PI 5-phosphatases SHIP2 or SKIP could be localized at the plasma membrane and can reduce either
PI(3,4,5)P3 or PI(4,5)P2 abundance. In the
glioblastoma 1321 N1 cells, SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration.