期刊
CANCER CELL
卷 31, 期 5, 页码 685-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2017.04.002
关键词
-
资金
- R01 grant from the National Cancer Institute and a Stein Innovation Award from Research to Prevent Blindness [CA142873]
- Gerson and Barbara Baker Distinguished Professorship
- Young Investigator Award from the Melanoma Research Alliance
- Sandler Program in Basic Science (start-up), NIH-NCI Physical Science Oncology Center grant [U54CA143874]
- NIH [1P01AI091580-01]
- Gabrielle's Angel Foundation
- UCSF ACS grant
- UCSF Research Allocation Program (RAP) pilot grant
- Eye Tumour Research Fund of the Royal Liverpool University Hospital
- Fight for Sight [1497/98] Funding Source: researchfish
Constitutive activation of G alpha q signaling by mutations in GNAQ or GNA11 occurs in over 80% of uveal melanomas (UMs) and activates MAPK. Protein kinase C (PKC) has been implicated as a link, but the mechanistic details remained unclear. We identified PKC delta and epsilon as required and sufficient to activate MAPK in GNAQ mutant melanomas. MAPK activation depends on Ras and is caused by RasGRP3, which is significantly and selectively overexpressed in response to GNAQ/11 mutation in UM. RasGRP3 activation occurs via PKC delta- and epsilon-dependent phosphorylation and PKC-independent, DAG-mediated membrane recruitment, possibly explaining the limited effect of PKC inhibitors to durably suppress MAPK in UM. The findings nominate RasGRP3 as a therapeutic target for cancers driven by oncogenic GNAQ/11.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据