Gene interactions and pathways from curated databases and text-mining
Blood 2008, PMID: 18025151

IL-2- and IL-15-induced activation of the rapamycin-sensitive mTORC1 pathway in malignant CD4+ T lymphocytes.

Marzec, Michal; Liu, Xiaobin; Kasprzycka, Monika; Witkiewicz, Agnieszka; Raghunath, Puthiyaveettil N; El-Salem, Mouna; Robertson, Erle; Odum, Niels; Wasik, Mariusz A

We examined functional status, activation mechanisms, and biologic role of the mTORC1 signaling pathway in malignant CD4(+) T cells derived from the cutaneous T-cell lymphoma (CTCL). Whereas the spontaneously growing CTCL-derived cell lines displayed persistent activation of the TORC1 as well as the PI3K/Akt and MEK/ERK pathways, the IL-2-dependent cell lines activated the pathways in response to IL-2 and IL-15 but not IL-21. Activation of mTORC1 and MEK/ERK was nutrient dependent. The mTORC1, PI3K/Akt, and MEK/ERK pathways could also be activated by IL-2 in the primary leukemic, mitogen-preactivated CTCL cells. mTORC1 activation was also detected in the CTCL tissues in the lymphoma stage-dependent manner with the highest percentage of positive cells present in the cases with a large cell transformation. Rapamycin inhibited mTORC1 signaling and suppressed CTCL cell proliferation but showed little effect on their apoptotic rate when used as a single agent. Activation of the mTORC1, PI3K/Akt, and MEK/ERK pathways was strictly dependent on the Jak3 and Jak1 kinases. Finally, mTORC1 activation was transduced preferentially through the PI3K/Akt pathway. These findings document the selective gammac-signaling cytokine-mediated activation of the mTORC1 pathway in the CTCL cells and suggest that the pathway represents a therapeutic target in CTCL and, possibly, other T-cell lymphomas.

Diseases/Pathways annotated by Medline MESH: Lymphoma, T-Cell, Cutaneous
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Text Mining Data

mTORC1 → IL-2: " The mTORC1 , PI3K/Akt, and MEK/ERK pathways could also be activated by IL-2 in the primary leukemic, mitogen preactivated CTCL cells "

PI3K/Akt → IL-2: " The mTORC1, PI3K/Akt , and MEK/ERK pathways could also be activated by IL-2 in the primary leukemic, mitogen preactivated CTCL cells "

PI3K/Akt → IL-2: " The mTORC1, PI3K/Akt , and MEK/ERK pathways could also be activated by IL-2 in the primary leukemic, mitogen preactivated CTCL cells "

Manually curated Databases

No curated data.