mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and Rapamycin-Reference-Cited by-同舟云学术

mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and Rapamycin

Published:2013-07-26 Issue:6144 Volume:341 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Kang Seong A.¹²,Pacold Michael E.¹²³⁴,Cervantes Christopher L.¹²,Lim Daniel⁵,Lou Hua Jane⁶,Ottina Kathleen¹²,Gray Nathanael S.³⁷,Turk Benjamin E.⁶,Yaffe Michael B.²⁵⁸,Sabatini David M.¹²⁵

Affiliation:

1. Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.

2. Department of Biology, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

3. Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA.

4. Department of Radiation Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.

5. David H. Koch Center for Integrative Cancer Research at MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

6. Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.

7. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

8. Department of Surgery, Beth Israel Deaconess Hospital, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.

Abstract

Not mTORCing Inhibition of the protein kinase complex mTORC1 has potentially beneficial therapeutic affects that include inhibition of cancer and extension of life span. However, effects of its inhibition in vivo have sometimes been disappointing. One reason may be that the well-studied inhibitor of mTORC1, rapamycin, inhibits some effects of mTORC1 but not others. In line with this idea, Kang et al. ( 1236566 ) show that the effect of rapamycin depends on the substrate. Characteristics of the phosphorylation sites on various substrates caused them to be phosphorylated with different efficiency by mTORC1. The substrates that were most efficiently phosphorylated were resistant to inhibition of mTORC1. The results explain how various sites, sometimes within the same protein, can differ in their sensitivity to rapamycin.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference49 articles.

1. mTOR Signaling in Growth Control and Disease

2. The Pharmacology of mTOR Inhibition

3. Rapamycin passes the torch: a new generation of mTOR inhibitors

4. A mammalian protein targeted by G1-arresting rapamycin–receptor complex

5. RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs

Cited by 394 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Modeling mTORopathy-related epilepsy in cultured murine hippocampal neurons using the multi-electrode array;Experimental Neurology;2024-09

2. Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles;Communications Biology;2024-08-10

3. PKD2 regulates autophagy and forms a protein complex with BECN1 at the primary cilium of hypothalamic neuronal cells;Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease;2024-08

4. Comparison the effect of autophagy inducer rapamycin concentrations on primary hepatic stellate cell activation;Gazzetta Medica Italiana Archivio per le Scienze Mediche;2024-08

5. New developments in AMPK and mTORC1 cross-talk;Essays in Biochemistry;2024-07-12