Skip to main content

FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity.

Publication ,  Journal Article
Cardenas, ME; Heitman, J
Published in: EMBO J
December 1, 1995

In complex with the immunophilin FKBP12, the natural product rapamycin inhibits signal transduction events required for G1 to S phase cell cycle progression in yeast and mammalian cells. Genetic studies in yeast first implicated the TOR1 and TOR2 proteins as targets of the FKBP12-rapamycin complex. We report here that the TOR2 protein is membrane associated and localized to the surface of the yeast vacuole. Immunoprecipitated TOR2 protein contains readily detectable phosphatidylinositol-4 (PI-4) kinase activity attributable to either a TOR2 intrinsic activity or to a PI-4 kinase tightly associated with TOR2. Importantly, we find that rapamycin stimulates FKBP12 binding to wild-type TOR2 but not to a rapamycin-resistant TOR2-1 mutant protein. Surprisingly, FKBP12-rapamycin binding does not markedly inhibit the PI kinase activity associated with TOR2, but does cause a delocalization of TOR2 from the vacuolar surface, which may deprive the TOR2-associated PI-4 kinase activity of its in vivo substrate. Several additional findings indicate that vacuolar localization is important for TOR2 function and, conversely, that TOR2 modulates vacuolar morphology and segregation. These studies demonstrate that TOR2 is an essential, highly conserved component of a signal transduction pathway regulating cell cycle progression conserved from yeast to man.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

December 1, 1995

Volume

14

Issue

23

Start / End Page

5892 / 5907

Location

England

Related Subject Headings

  • Vacuoles
  • Tacrolimus Binding Proteins
  • Sirolimus
  • Signal Transduction
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Recombinant Fusion Proteins
  • Protein Binding
  • Precipitin Tests
  • Polyenes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cardenas, M. E., & Heitman, J. (1995). FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity. EMBO J, 14(23), 5892–5907. https://doi.org/10.1002/j.1460-2075.1995.tb00277.x
Cardenas, M. E., and J. Heitman. “FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity.EMBO J 14, no. 23 (December 1, 1995): 5892–5907. https://doi.org/10.1002/j.1460-2075.1995.tb00277.x.
Cardenas, M. E., and J. Heitman. “FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity.EMBO J, vol. 14, no. 23, Dec. 1995, pp. 5892–907. Pubmed, doi:10.1002/j.1460-2075.1995.tb00277.x.

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

December 1, 1995

Volume

14

Issue

23

Start / End Page

5892 / 5907

Location

England

Related Subject Headings

  • Vacuoles
  • Tacrolimus Binding Proteins
  • Sirolimus
  • Signal Transduction
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Recombinant Fusion Proteins
  • Protein Binding
  • Precipitin Tests
  • Polyenes