1932

Abstract

Precise control of the balance between protein phosphorylation, catalyzed by protein kinases, and protein dephosphorylation, catalyzed by protein phosphatases, is essential for cellular homeostasis. Dysregulation of this balance leads to pathophysiological states, driving diseases such as cancer, heart disease, and diabetes. Aberrant phosphorylation of components of the pathways that control cell growth and cell survival are particularly prevalent in cancer. One of the most studied tumor suppressors in these pathways is the lipid phosphatase PTEN (hosphatase and sin homolog deleted on chromosome ), which dephosphorylates the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP), thus preventing activation of the oncogenic kinase AKT (v-akt murine thymoma viral oncogene homolog). In 2005, the discovery of a family of protein phosphatases whose members directly dephosphorylate and inactivate AKT introduced a new negative regulator of the phosphoinositide 3-kinase (PI3K) oncogenic pathway. leckstrin omology domain eucine-rich repeat rotein hosphatase (PHLPP) isozymes comprise a novel tumor suppressor family whose two members, PHLPP1 and PHLPP2, are deleted as frequently as PTEN in cancers such as those of the prostate. PHLPP is thus a novel therapeutic target to suppress oncogenic pathways and is a potential candidate biomarker to stratify patients for the appropriate targeted therapeutics. This review discusses the role of PHLPP in terminating AKT signaling and how pharmacological intervention would impact this pathway.

Keyword(s): AKTp53PHLPPPI3KPTEN
Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-011112-140338
2014-01-06
2024-06-20
Loading full text...

Full text loading...

/content/journals/10.1146/annurev-pharmtox-011112-140338
Loading
/content/journals/10.1146/annurev-pharmtox-011112-140338
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error