期刊
CELLULAR SIGNALLING
卷 26, 期 9, 页码 1950-1957出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2014.05.011
关键词
Rheb GTPase; mTORC1; Lysosome; Mouse study; Structure; Mutants
类别
资金
- NIH [CA41996]
In this review we highlight recent progress in the study of Rheb family GTPases. Structural studies using X-ray crystallography and NMR have given us insight into unique features of this GTPase. Combined with mutagenesis studies, these works have expanded our understanding of residues that affect Rheb GTP/GDP bound ratios, effector protein interactions, and stimulation of mTORC1 signaling. Analysis of cancer genome databases has revealed that several human carcinomas contain activating mutations of the protein. Rheb's role in activating mTORC1 signaling at the lysosome in response to stimuli has been further elucidated. Rheb has also been suggested to play roles in other cellular pathways including mitophagy and peroxisomal ROS response. A number of studies in mice have demonstrated the importance of Rheb in development, as well as in a variety of functions including cardiac protection and myelination.We conclude with a discussion of future prospects in the study of Rheb family GTPases. (C) 2014 Elsevier Inc. All rights reserved.
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