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Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases.
Biochem Soc Trans. 2016 Feb; 44(1):240-52.BS

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+Show Affiliations

Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia christina.mitchell@monash.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26862211

Citation

Eramo, Matthew J., and Christina A. Mitchell. "Regulation of PtdIns(3,4,5)P3/Akt Signalling By Inositol Polyphosphate 5-phosphatases." Biochemical Society Transactions, vol. 44, no. 1, 2016, pp. 240-52.
Eramo MJ, Mitchell CA. Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases. Biochem Soc Trans. 2016;44(1):240-52.
Eramo, M. J., & Mitchell, C. A. (2016). Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases. Biochemical Society Transactions, 44(1), 240-52. https://doi.org/10.1042/BST20150214
Eramo MJ, Mitchell CA. Regulation of PtdIns(3,4,5)P3/Akt Signalling By Inositol Polyphosphate 5-phosphatases. Biochem Soc Trans. 2016;44(1):240-52. PubMed PMID: 26862211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases. AU - Eramo,Matthew J, AU - Mitchell,Christina A, PY - 2016/2/11/entrez PY - 2016/2/11/pubmed PY - 2016/11/1/medline KW - 5-phosphatase KW - Akt signalling KW - breast cancer KW - developmental disease KW - phosphoinositide 3-kinase KW - phosphoinositides SP - 240 EP - 52 JF - Biochemical Society transactions JO - Biochem Soc Trans VL - 44 IS - 1 N2 - 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. SN - 1470-8752 UR - https://www.unboundmedicine.com/medline/citation/26862211/Regulation_of_PtdIns_345_P3/Akt_signalling_by_inositol_polyphosphate_5_phosphatases_ L2 - https://portlandpress.com/biochemsoctrans/article-lookup/doi/10.1042/BST20150214 DB - PRIME DP - Unbound Medicine ER -