PMID: 8595879Feb 1, 1996Paper

Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast

Genes & Development
C M AlarconJ Heitman

Abstract

In complex with the prolyl isomerase FKBP12, the natural product rapamycin blocks signal transduction in organisms as diverse as yeast and man. The yeast targets of FKBP12-rapamycin, TOR1 and TOR2, are large proteins with homology to lipid and protein kinases. A mammalian FKBP12-rapamycin binding protein, RAFT1, shares 39% and 43% identity with TOR1 and TOR2 proteins, respectively but has not been linked to rapamycin action in vivo. We find that when expressed in yeast, neither wild-type nor mutant RAFT1 complemented tor mutations or conferred rapamycin resistance. In contrast, TOR1-RAFT1 and TOR1-RAFT1 hybrid proteins containing the carboxy-terminal RAFT1 kinase domain complemented tor2 and tor1 mutant strains, respectively. Moreover, TOR2-RAFT1 and TOR1-RAFT1 hybrid proteins mutated at the position corresponding to rapamycin-resistant TOR mutants (S20351) conferred rapamycin resistance. Like the TOR2 protein, the TOR2-RAFT1 proteins were stably expressed, localized to the vacuolar surface, and associated with a phosphatidylinositol-4 kinase activity. These findings directly link the mammalian TOR homolog RAFT1 to rapamycin action in vivo and indicate that the TOR/RAFT1 kinase domain has been functionally conserved from yeast ...Continue Reading

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Citations

Nov 10, 1998·Trends in Biotechnology·M E CardenasJ Heitman
Dec 2, 1999·Molecular and Cellular Endocrinology·N S CutlerM E Cardenas
Aug 19, 2000·The Biochemical Journal·W E HughesP J Parker
Apr 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Rekha PuriaMaria E Cardenas
Dec 12, 2001·Molecular Biology of the Cell·N S CutlerM E Cardenas
May 15, 1997·The EMBO Journal·A OdomJ Heitman
Jan 5, 2000·Genes & Development·M E CardenasJ Heitman
Sep 25, 2010·BMC Genomics·Cecelia A ShertzMaria E Cardenas
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·John L Nitiss
Oct 12, 2018·Journal of Applied Microbiology·M ZhangS Sun
Oct 23, 1997·The Journal of Biological Chemistry·K HaraJ Avruch
Mar 27, 2001·The Journal of Biological Chemistry·J RohdeM E Cardenas
Sep 25, 2008·The Journal of Biological Chemistry·Yoichiro OhneTatsuya Maeda

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