Curr Mol Med 2005,
PMID: 16305491
Giles, Francis J; Albitar, Maher
Reflecting its critical role in integrating cell growth and division with the cellular nutritional environment, the mammalian target of rapamycin *(mTOR) is a highly conserved downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B) signaling pathway. mTOR activates both the 40S ribosomal protein S6 kinase (p70s6k) and the eukaryotic initiation factor 4E-binding protein-1. As a consequence of inhibiting its downstream messengers, mTOR inhibitors prevent cyclin-dependent kinase (CDK) activation, inhibit retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1, leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help cause GI phase arrest. Constitutive activation of the PI3K/Akt kinases occur in human leukemias. FLT3, VEGF, and BCR-ABL mediate their activities via mTOR. New rapamycin analogs including CCI-779, RAD001, and AP23573, are entering clinical studies for patients with hematologic malignancies.
Diseases/Pathways annotated by Medline MESH: Hematologic Neoplasms, Leukemia
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Text Mining Data
cyclin dependent kinase (CDK) → mTOR: "
As a consequence of inhibiting its downstream messengers,
mTOR inhibitors
prevent cyclin dependent kinase (CDK) activation, inhibit retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1, leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help cause GI phase arrest
"
BCR-ABL → FLT3: "
FLT3 , VEGF, and BCR-ABL mediate their activities via mTOR
"
BCR-ABL → FLT3: "
FLT3 , VEGF, and BCR-ABL mediate their activities via mTOR
"
Manually curated Databases
No curated data.