Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression

@article{Kunz1993TargetOR,
  title={Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression},
  author={J. Kunz and R. Henr{\'i}quez and U. Schneider and M. Deuter‐Reinhard and N. Movva and M. Hall},
  journal={Cell},
  year={1993},
  volume={73},
  pages={585-596}
}
The yeast TOR2 gene encodes an essential 282 kd phosphatidylinositol (PI) 3-kinase homolog. TOR2 is related to the catalytic subunit of bovine PI 3-kinase and to yeast VPS34, a vacuolar sorting protein also shown to have PI 3-kinase activity. The immunosuppressant rapamycin most likely acts by inhibiting PI kinase activity because TOR2 mutations confer resistance to rapamycin and because a TOR1 TOR2 double disruption (TOR1 is a nonessential TOR2 homolog) confers G1 arrest, as does rapamycin… Expand
TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin
TLDR
FKBP12-rapamycin does not appear to inhibit the kinase activity of TOR proteins in a general way; instead, it may interfere selectively with TOR protein binding to or phosphorylation of G1 effectors. Expand
TOR kinase homologs function in a signal transduction pathway that is conserved from yeast to mammals
TLDR
Findings indicate that the TOR proteins function in a signal transduction pathway that coordinates nutritional and mitogenic signals to control protein biosynthesis and degradation. Expand
FKBP12‐rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol‐4 kinase activity.
TLDR
It is reported here that the TOR2 protein is membrane associated and localized to the surface of the yeast vacuole, and it is demonstrated that TOR2 is an essential, highly conserved component of a signal transduction pathway regulating cell cycle progression conserved from yeast to man. Expand
TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast.
TLDR
TOR1 and TOR2 are likely similar but not identical, rapamycin-sensitive PI kinases possibly regulated by phosphorylation, and may be components of a novel signal transduction pathway controlling progression through G1. Expand
TOR Signaling in Budding Yeast
TOR (Target of Rapamycin) is a Ser/Thr kinase that was originally identified by genetic screening using the budding yeast Saccharomyces cerevisiae. The TOR protein forms two structurally andExpand
Protein kinase activity and identification of a toxic effector domain of the target of rapamycin TOR proteins in yeast.
TLDR
The findings identify a toxic effector domain of the TOR proteins that may interact with substrates or regulators of theTOR kinase cascade and that shares sequence identity with other PIK family members, including ATR, Rad3, Mei-41, and ATM. Expand
RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex.
  • M. I. Chiu, H. Katz, V. Berlin
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1994
TLDR
Using a two-hybrid system, mammalian clones that interact with the human FK506/rapamycin-binding protein (FKBP12) in the presence of rapamycin are isolated and specific interactors, designated RAPT1, encode overlapping sequences homologous to yeast Tor, a putative novel phosphatidylinositol 3-kinase. Expand
Signaling by Target of Rapamycin Proteins in Cell Growth Control
TLDR
The discovery that the small GTPase Rheb is a direct downstream target of TSC1-TSC2 and a positive regulator of the TOR function has significantly advanced the understanding of the molecular mechanism of TOR activation. Expand
The Rapamycin and FKBP12 Target (RAFT) Displays Phosphatidylinositol 4-Kinase Activity (*)
TLDR
It is shown that RAFT1, immunoprecipitated from rat brain and MG63 and HEK293 cells, contains PI 4-kinase activity and that rapamycin-FKBP12 has no effect on this activity. Expand
Regulation of TORC2 function and localization by Rab5 GTPases in Saccharomyces cerevisiae
TLDR
It was demonstrated both in vivo and in vitro that the GTP-bound state of the Rab5 GTPase Vps21/Ypt51 physically associates withTORC2 and acts as a direct positive effector required for full TORC2 activity, providing a self-reinforcing control circuit for sustained up-regulation of TORC 2-Ypk1 signaling. Expand
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References

SHOWING 1-10 OF 87 REFERENCES
Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting.
TLDR
Overexpression of VPS34p resulted in an increase in PI 3-kinase activity, and this activity was specifically precipitated with antisera to Vps34p. Expand
Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast
TLDR
Nonallelic noncomplementation between FPR1, TOR1, and TOR2 alleles suggests that the products of these genes may interact as subunits of a protein complex that may mediate nuclear entry of signals required for progression through the cell cycle. Expand
A family of cyclin homologs that control the G1 phase in yeast.
Two Saccharomyces cerevisiae genes were isolated based upon their dosage-dependent rescue of a temperature-sensitive mutation of the gene CDC28, which encodes a protein kinase involved in control ofExpand
Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases
TLDR
These studies identify a rapamycin-sensitive signaling pathway, argue for a ubiquitous role for FKBPs in signal transduction, indicate that FK506-FKBP-calcineurin complexes do not interfere with pp70S6K signaling, and show that in fibroblasts pp70 S6K, not RSK, is the physiological S6 kinase. Expand
An essential G1 function for cyclin-like proteins in yeast
TLDR
Using strains where CLN1 was expressed conditionally, the essential function of ClN proteins was found to be limited to the G1 phase, consistent with the hypothesis that Cln proteins activate the Cdc28 protein kinase, shown to be essential for the G 1 to S phase transition in S. cerevisiae. Expand
Essential role for phosphatidylinositol 4,5-bisphosphate in yeast cell proliferation
TLDR
A monoclonal antibody specific for PIP2 is developed and reported that it inhibits mitogenesis of mammalian cells stimulated by platelet-derived growth factor and bombesin12, and it is reported that when introduced into yeast cells by electroporation this antibody inhibits their growth. Expand
FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation
TLDR
The suppression of a gpa1 null (G alpha subunit) by a fus3 null also suggests FUS3 is in the signal transduction pathway, which suggests it has a positive role in conjugation. Expand
Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase.
TLDR
The immunosuppressant rapamycin inhibited proliferation of the H4IIEC hepatoma cell line and inhibited the appearance of the hyperphosphorylated form of p70 S6 kinase concomitant with the inhibition of enzyme activity toward 40S subunits. Expand
Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase
TLDR
The selective blockade of the p70 S6 kinase activation cascade by the rapamycin–FKBP complex implicates this signalling pathway in the regulation of T cell entry into S phase. Expand
Phosphatidylinositol 3-kinase and its novel product, phosphatidylinositol 3-phosphate, are present in Saccharomyces cerevisiae.
TLDR
The conservation of the enzymatic activity from yeast to man suggests that it has an important functional role in the cell cycle. Expand
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