|
KMID : 0613820180280091100
|
|
Journal of Life Science
2018 Volume.28 No. 9 p.1100 ~ p.1117
|
|
|
Ras GTPases and Ras GTPase Activating Proteins (RasGAPs) in Human Disease
|
|
Jang Jong-Soo
|
|
|
Abstract
|
|
|
|
The Ras superfamily of small G-proteins acts as a molecular switch on the intracellular signaling pathway. Upon ligand stimulation, inactive GTPases (Ras-GDP) are activated (Ras-GTP) using guanine nucleotide exchange factor (GEF) and transmit signals to their downstream effectors. Following signal transmission, active Ras-GTP become inactive Ras-GDP and cease signaling. However, the intrinsic GTPase activity of Ras proteins is weak, requiring Ras GTPase-activating protein (RasGAP) to efficiently convert RAS-GTP to Ras-GDP. Since deregulation of the Ras pathway is found in nearly 30% of all human cancers, it might be useful to clarify the structural and physiological roles of Ras GTPases. Recently, RasGAP has emerged as a new class of tumor-suppressor protein and a potential therapeutic target for cancer. Therefore, it is important to clarify the physiological roles of the individual GAPs in human diseases. The first RasGAP discovered was RASA1, also known as p120 RasGAP. RASA1 is widely expressed, independent of cell type and tissue distribution. Subsequently, neurofibromatosis type 1 (NF1) was discovered. The remaining GAPs are affiliated with the GAP1 and synaptic GAP (SynGAP) families. There are more than 170 Ras GTPases and 14 Ras GAP members in the human genome. This review focused on the current understanding of Ras GTPase and RasGAP in human diseases, including cancers.
|
|
|
KEYWORD
|
|
|
NF1, RASA1, RasGAP, Ras GTPase, tumor suppressor
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|