The main focus of this application is on the functions of G-proteins in endothelial cells. G-protein G?13 is critical for blood vessel formation. This proposal builds on our discovery of a novel mechanism by which G?13 functions through SOS, a direct regulator of Ras and the new observation that endothelial cell-specific deletion of G?13 impairs organ regeneration.
The first aim i s to dissect the biochemical mechanism by which G?13 regulates SOS in vitro.
The second aim i s to determine how G?13 and G-protein- coupled receptors regulate SOS in cells.
The third aim i s to investigate the impact of endothelial cell-specific deletion of SOS1 on organ regeneration.

Public Health Relevance

This research is directly related to human health. Endothelial cells are essential for angiogenesis and vascular development. Therefore, a better understanding of the regulatory mechanisms of endothelial functions will advance our combat against many human diseases such as cardiovascular diseases and cancers.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL130478-03
Application #
9475699
Study Section
Vascular Cell and Molecular Biology Study Section (VCMB)
Program Officer
Gao, Yunling
Project Start
2016-06-01
Project End
2020-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Physiology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Wang, Limin; Wang, Dawei; Xing, Bowen et al. (2017) G-Protein G?13 Functions with Abl Kinase to Regulate Actin Cytoskeletal Reorganization. J Mol Biol 429:3836-3849
Syrovatkina, Viktoriya; Alegre, Kamela O; Dey, Raja et al. (2016) Regulation, Signaling, and Physiological Functions of G-Proteins. J Mol Biol 428:3850-68