TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin

Xiao Feng Zheng, David Fiorentino, Jie Chen, Gerald R. Crabtree, Stuart L. Schreiber

Research output: Contribution to journalArticlepeer-review

Abstract

The rapamycin-sensitive signaling pathway is required to transduce specific mitogenic signals to the cell cycle machinery responsible for G1 progression. Genetic studies in yeast identified two related genes on this pathway, TOR1 and TOR2, thought to encode novel phosphatidyllnositol kinases. We now show that an intact kinase domain Is required for the G1 cell cycle functions of both proteins, for the ability of a mutation in a neighboring FKBP12-rapamycin-binding domain of the TOR1 protein to inhibit the growth of yeast cells when overexpressed, and for the essential function of the TOR2 protein. The G1 function of both TOR proteins is sensitive to rapamycin, but the essential function of TOR2 is not. Thus, 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.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
JournalCell
Volume82
Issue number1
DOIs
StatePublished - Jul 14 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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