Gene interactions and pathways from curated databases and text-mining
Eur J Immunol 2007, PMID: 17724683

Distinct signaling mechanisms activate the target of rapamycin in response to different B-cell stimuli.

Donahue, Amber C; Fruman, David A

Phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR), a downstream kinase, are both required for proliferation of splenic B cells. However, the functions of PI3K and mTOR in response to different stimuli and among B cell subsets have not been fully elucidated. We used flow cytometry and magnetic cell sorting to examine the requirement for PI3K and mTOR in responses of splenic B cell subsets to BCR and LPS stimulation. BCR-mediated phosphorylation of Akt and Erk is sensitive to the PI3K catalytic inhibitor wortmannin in both marginal zone (MZ) and follicular (FO) cells. BCR-mediated mTOR activation in both subsets is inhibited by wortmannin, though less strongly in MZ cells. In contrast, LPS-induced mTOR signaling is strikingly resistant to wortmannin in both subsets. Similarly, functional responses to LPS are partially wortmannin resistant yet sensitive to mTOR inhibition by rapamycin. We also observed mitogen-independent mTOR activity that is regulated by nutrient availability, and is significantly elevated in MZ cells relative to FO cells. These data define both similarities and differences in PI3K/mTOR signaling mechanisms in MZ and FO cells, and suggest that mTOR signaling can occur in the absence of PI3K activation to promote B cell responses to LPS.

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Text Mining Data

mTOR → BCR: " We used flow cytometry and magnetic cell sorting to examine the requirement for PI3K and mTOR in responses of splenic B cell subsets to BCR and LPS stimulation "

mTOR → LPS: " We used flow cytometry and magnetic cell sorting to examine the requirement for PI3K and mTOR in responses of splenic B cell subsets to BCR and LPS stimulation "

PI3K → BCR: " We used flow cytometry and magnetic cell sorting to examine the requirement for PI3K and mTOR in responses of splenic B cell subsets to BCR and LPS stimulation "

PI3K → LPS: " We used flow cytometry and magnetic cell sorting to examine the requirement for PI3K and mTOR in responses of splenic B cell subsets to BCR and LPS stimulation "

Erk → BCR: " BCR mediated phosphorylation of Akt and Erk is sensitive to the PI3K catalytic inhibitor wortmannin in both marginal zone ( MZ ) and follicular ( FO ) cells "

Akt → BCR: " BCR mediated phosphorylation of Akt and Erk is sensitive to the PI3K catalytic inhibitor wortmannin in both marginal zone ( MZ ) and follicular ( FO ) cells "

mTOR → BCR: " BCR mediated mTOR activation in both subsets is inhibited by wortmannin, though less strongly in MZ cells "

mTOR signaling → LPS: " In contrast, LPS induced mTOR signaling is strikingly resistant to wortmannin in both subsets "

Manually curated Databases

No curated data.