# NIH grant: The function of PTEN (1R01GM155592-01A1) — retained record

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source: [us-gov-api](https://highsignal.app/data/us-gov-api) (us-gov-api:nih-reporter)  published 2026-07-16 00:00 ingested 2026-07-20 08:52

[original source ↗](https://reporter.nih.gov/project-details/1R01GM155592-01A1)

## retained text



```
NIH grant 1R01GM155592-01A1: The function of PTEN
Institute: {'code': 'GM', 'abbreviation': 'NIGMS', 'name': 'National Institute of General Medical Sciences', 'admin_org_id': '12500024', 'admin_funding_url': ''}. PI: LINDSEY D MAYO. Award: $380990.
Start: 2026-07-16T00:00:00.
PROJECT ABSTRACT
The Phosphatase and tensin homolog (PTEN) protein is a dual-specificity phosphatase. Mutations in PTEN are
found in inherited PTEN-related Proteus syndrome, an overarching syndrome encompassing Bannayan-Riley-
Ruvalcaba syndrome (BRRS), hamartoma tumor syndrome, and Cowden's syndrome. These syndromes are
associated clinically with the overgrowth of numerous tissues, including skin, adipose, central nervous system
skeletal, and microencephaly. PTEN somatic mutations are also found in numerous tumor types associated with
progressive disease. The activity of PTEN is associated with the dephosphorylation of the second messenger
phosphatidyl inositol 3,4,5 phosphate to regulate the PI3K-PIP3-Akt pathway. What remains to be determined is
how is the catalytic domain of PTEN is regulated by phosphorylation and activated by DNA damage kinases,
whether activation will be required for induction of apoptotic genes and are there specific mutants in the catalytic
domain that convert PTEN to a protein phosphatase that activates signaling pathways to promote proliferation.
Our preliminary data addresses gaps in our knowledge and shows that a DNA damage-activated kinase
phosphorylates PTEN in the catalytic domain, which converts PTEN to protein phosphatase. We identified a
novel substrate that is activated to induce apoptotic genes. We analyzed some of the inherited mutations of
PTEN. We found that some of these mutants activate kinase signaling pathways in the cytoplasm that block cell
cycle checkpoints, permitting cell growth. One observation seen in patients with these hereditary syndromes and
cancers is highly proliferative cells. We will test our hypothesis: PTEN protein phosphatase activity is important
for cellular processes. We will test the hypothesis through two specific aims: 1. Determine how wild-type PTEN
catalytic activity is converted to a protein phosphatase to activate cell death, and 2. Determine how the mutant
PTEN can promote cell cycle progression. The gain in knowledge in the regulation of PTEN catalytic activity will
provide insight into normal and abnormal activity that regulates cellular outcome.
```



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