Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases.
Biochem Soc Trans
; 44(1): 240-52, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26862211
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fosfatos de Fosfatidilinositol
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Monoéster Fosfórico Hidrolases
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Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biochem Soc Trans
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Austrália