# Understanding G alpha q/11 localization and trafficking in uveal melanoma

> **NIH NIH F31** · THOMAS JEFFERSON UNIVERSITY · 2020 · $45,520

## Abstract

Project Summary/Abstract
Uveal melanoma is the most common intraocular tumor malignancy in adults, however no
effective therapies are available for metastatic uveal melanoma patients. This results in an
average survival of 2-8 months. Constitutively active mutations in Gαq and Gα11 have been
reported in up to 83% of uveal melanomas, however no inhibitors are available for constitutively
active Gαq or Gα11. The purpose of this study is to (1) understand the role of palmitoylation in
localization and signaling of constitutively active Gαq/11 in uveal melanoma cells and (2) to
determine if targeting palmitoylation of Gαq/11 can prevent Gαq/11-dependent signaling and
growth. Using immunofluorescence microscopy and cellular fractionation of HEK 293 cells and
uveal melanoma cells, constitutively active GαqQ209L shows decreased localization at
membranes compared to wild type Gαq, suggesting increased turnover of attached palmitate.
Moreover, a palmitoylation-deficient GαqQ209L displays a complete loss of plasma membrane
localization and an inability to signal as measured by YAP translocation into the nucleus, TEAD-
dependent luciferase activity, and ERK phosphorylation. The loss of signaling in the
palmitoylation-deficient mutant may result from its inability to localize to membranes. These
studies demonstrate that palmitoylation of mutationally activated Gαq/11 is required for its
signaling functions, providing a novel target to consider for inhibition of activated Gαq/11 in
uveal melanoma.

## Key facts

- **NIH application ID:** 9841909
- **Project number:** 5F31CA224803-03
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Clinita Randolph
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841909

## Citation

> US National Institutes of Health, RePORTER application 9841909, Understanding G alpha q/11 localization and trafficking in uveal melanoma (5F31CA224803-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9841909. Licensed CC0.

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