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The Saccharomyces cerevisiae targets of rapamycin, TOR1 and TOR2, signal activation of cell growth in response to nutrient availability. Loss of TOR or rapamycin treatment causes yeast cells to arrest growth in early G1 and to express several other physiological properties of starved (G0) cells. As part of this starvation response, high affinity amino acid(More)
The Saccharomyces cerevisiae genes TOR1 and TOR2 were originally identified by mutations that confer resistance to the immunosuppressant rapamycin. TOR2 was previously shown to encode an essential 282-kDa phosphatidylinositol kinase (PI kinase) homologue. The TOR1 gene product is also a large (281 kDa) PI kinase homologue, with 67% identity to TOR2. TOR1 is(More)
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(More)
The Saccharomyces cerevisiae gene TOR2 encodes a putative phosphatidylinositol kinase that has two essential functions. One function is redundant with TOR1, a TOR2 homolog, and is required for signaling translation initiation and early G1 progression. The second essential function is unique to TOR2. Here we report that loss of the TOR2-unique function(More)
The subcellular distribution of Tor1p and Tor2p, two phosphatidylinositol kinase homologs and targets of the immunosuppressive drug rapamycin in Saccharomyces cerevisiae, was analyzed. We found that Tor protein is peripherally associated with membranes. Subcellular fractionation and immunofluorescence studies showed that Tor1p and Tor2p associate with the(More)
The mechanisms of action of the immunosuppressive drugs cyclosporin A (CsA), FK506 and rapamycin are strikingly conserved from yeast to human T cells. Recent results obtained with yeast corroborate calcineurin as the target of CsA-cyclophilin and FK506-FKBP complexes, and reveal a phosphatidylinositol 3-kinase homologue as the target of the rapamycin-FKBP(More)
The immunosuppressants cyclosporin A, FK506, and rapamycin inhibit growth of unicellular eukaryotic microorganisms and also block activation of T lymphocytes from multicellular eukaryotes. In vitro, these compounds bind and inhibit two different types of peptidyl-prolyl cis-trans isomerases. Cyclosporin A binds cyclophilins, whereas FK506 and rapamycin bind(More)
Mutations in the coding region of the TWIST gene (encoding a basic helix-loop-helix transcription factor) have been identified in some cases of Saethre-Chotzen syndrome. Haploinsufficiency appears to be the pathogenic mechanism involved. To investigate the possibility that complete deletions of the TWIST gene also contribute to this disorder, we have(More)
The Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with uni- or bilateral coronal synostosis and mild limb deformities. It is caused by loss-of-function mutations of the TWIST 1 gene. In an attempt to delineate functional features separating SCS from Muenke's syndrome, we screened patients presenting with coronal suture(More)
The HER2/neu oncogene encodes a transmembrane protein that possesses intrinsic tyrosine kinase activity. Its overexpression has been associated with the malignant phenotype. In this study we examined HER2/neu expression in the normal and cancerous human pancreas. In the normal pancreas HER2/neu immunostaining was observed in acinar and ductal cells.(More)