Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases.

Abstract

The phosphoinositide 3-kinase (PI3K) generated lipid signals, PtdIns(3,4,5)P3 and PtdIns(3,4)P2, are both required for the maximal activation of the serine/threonine kinase proto-oncogene Akt. The inositol polyphosphate 5-phosphatases (5-phosphatases) hydrolyse the 5-position phosphate from the inositol head group of PtdIns(3,4,5)P3 to yield PtdIns(3,4)P2. Extensive work has revealed several 5-phosphatases inhibit PI3K-driven Akt signalling, by decreasing PtdIns(3,4,5)P3 despite increasing cellular levels of PtdIns(3,4)P2. The roles that 5-phosphatases play in suppressing cell proliferation and transformation are slow to emerge; however, the 5-phosphatase PIPP [proline-rich inositol polyphosphate 5-phosphatase; inositol polyphosphate 5-phosphatase (INPP5J)] has recently been identified as a putative tumour suppressor in melanoma and breast cancer and SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] inhibits haematopoietic cell proliferation. INPP5E regulates cilia stability and INPP5E mutations have been implicated ciliopathy syndromes. This review will examine 5-phosphatase regulation of PI3K/Akt signalling, focussing on the role PtdIns(3,4,5)P3 5-phosphatases play in developmental diseases and cancer.

• Authors: Matthew J Eramo, Christina A Mitchell
• Journal: Biochemical Society transactions (Biochem Soc Trans) Vol. 44 Issue 1 Pg. 240-52 (Feb 2016) ISSN: 1470-8752 [Electronic] England
• PMID: 26862211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2016 Authors; published by Portland Press Limited.

Chemical References

• MAS1 protein, human
• Phosphatidylinositol Phosphates
• Proto-Oncogene Mas
• phosphatidylinositol 3,4,5-triphosphate
• Proto-Oncogene Proteins c-akt
• Phosphoric Monoester Hydrolases
• Inositol Polyphosphate 5-Phosphatases
• INPP5D protein, human
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases

Topics

• Animals
• Cilia (metabolism)
• Humans
• Inositol Polyphosphate 5-Phosphatases
• Organ Specificity
• Phosphatidylinositol Phosphates (metabolism)
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
• Phosphoric Monoester Hydrolases (metabolism)
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction