The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease

Ooms, Lisa M., Horan, Kristy A., Rahman, Parvin, Seaton, Gillian, Gurung, Rajendra, Kethesparan, Dharini S. and Mitchell, Christina A.. 2009. The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease. Biochemical Journal 419 (1) , pp. 29-49. 10.1042/BJ20081673

Full text not available from this repository.

Abstract

Phosphoinositides are membrane-bound signalling molecules that regulate cell proliferation and survival, cytoskeletal reorganization and vesicular trafficking by recruiting effector proteins to cellular membranes. Growth factor or insulin stimulation induces a canonical cascade resulting in the transient phosphorylation of PtdIns(4,5)P2 by PI3K (phosphoinositide 3-kinase) to form PtdIns(3,4,5)P3, which is rapidly dephosphorylated either by PTEN (phosphatase and tensin homologue deleted on chromosome 10) back to PtdIns(4,5)P2, or by the 5-ptases (inositol polyphosphate 5-phosphatases), generating PtdIns(3,4)P2. The 5-ptases also hydrolyse PtdIns(4,5)P2, forming PtdIns4P. Ten mammalian 5-ptases have been identified, which share a catalytic mechanism similar to that of the apurinic/apyrimidinic endonucleases. Gene-targeted deletion of 5-ptases in mice has revealed that these enzymes regulate haemopoietic cell proliferation, synaptic vesicle recycling, insulin signalling, endocytosis, vesicular trafficking and actin polymerization. Several studies have revealed that the molecular basis of Lowe's syndrome is due to mutations in the 5-ptase OCRL (oculocerebrorenal syndrome of Lowe). Futhermore, the 5-ptases SHIP [SH2 (Src homology 2)-domain-containing inositol phosphatase] 2, SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) and 72-5ptase (72 kDa 5-ptase)/Type IV/Inpp5e (inositol polyphosphate 5-phosphatase E) are implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues. SHIP2 polymorphisms are associated with a predisposition to insulin resistance. Gene profiling studies have identified changes in the expression of various 5-ptases in specific cancers. In addition, 5-ptases such as SHIP1, SHIP2 and 72-5ptase/Type IV/Inpp5e regulate macrophage phagocytosis, and SHIP1 also controls haemopoietic cell proliferation. Therefore the 5-ptases are a significant family of signal-modulating enzymes that govern a plethora of cellular functions by regulating the levels of specific phosphoinositides. Emerging studies have implicated their loss or gain of function in human disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	cancer, diabetes, inflammation, Lowe's syndrome, 5-phosphatase, phosphoinositide.
Publisher:	Biochemical Society
ISSN:	0264-6021
Last Modified:	04 Jun 2017 07:46
URI:	https://orca.cardiff.ac.uk/id/eprint/67833

Citation Data

Cited 180 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item