The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse
Open accessAbstract
The FKBP-12-rapamycin associated protein (FRAP, also known as mTOR and RAFT-1) is a member of the phosphoinositide kinase related kinase family. FRAP has serine/threonine kinase activity and mediates the cellular response to mitogens through signaling to p70s6 kinase (p70 s6k ) and 4E-BP1, resulting in an increase in translation of subsets of cellular mRNAs. Translational up-regulation is blocked by inactivation of FRAP signaling by rapamycin, resulting in G 1 cell cycle arrest. Rapamycin is used as an immunosuppressant for kidney transplants and is currently under investigation as an antiproliferative agent in tumors because of its ability to block FRAP activity. Although the role of FRAP has been extensively studied in vitro , characterization of mammalian FRAP function in vivo has been limited to the immune system and tumor models. Here we report the identification of a loss-of-function mutation in the mouse FRAP gene, which illustrates a requirement for FRAP activity in embryonic development. Our studies also determined that rapamycin treatment of the early embryo results in a phenotype indistinguishable from the FRAP mutant, demonstrating that rapamycin has teratogenic activity.
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Citations
Cites
Regulation of translation initiation by FRAP/mTOR
Gingras, A.-C., Raught, B., & Sonenberg, N. (2001) · Genes & Development · doi:10.1101/gad.887201 · Cited by 1,545
Self-citationVilella-Bach, M., Nuzzi, P., Fang, Y., & Chen, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.7.4266 · Cited by 154
Cited by
Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., & Hall, M. N. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00636-6 · Cited by 1,886
The tor pathway: a target for cancer therapy
Bjornsti, M.-A., & Houghton, P. J. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1362 · Cited by 1,314
Fingar, D. C., & Blenis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207542 · Cited by 1,247
Heras-Sandoval, D., Pérez-Rojas, J. M., Hernández-Damián, J., & Pedraza-Chaverri, J. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.08.019 · Cited by 1,091
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes & Development · doi:10.1101/gad.995802 · Cited by 1,093
Metadata
- Authors
- Hentges, K. E., Sirry, B., Gingeras, A.-C., Sarbassov, D., Sonenberg, N., Sabatini, D., & Peterson, A. S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-11-13
- Volume
- 98
- Issue
- 24
- Pages
- 13796-13801
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2168375708
- Cited by
- 171
- References
- 2
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- green
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- Hentges, K. E., Sirry, B., Gingeras, A.-C., Sarbassov, D., Sonenberg, N., Sabatini, D., & Peterson, A. S. (2001). FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.241184198
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