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BCR ➞ MTOR (1 - 4 of 4)
PMID: 17724683
Distinct signaling mechanisms activate the target of rapamycin in response to different B-cell stimuli. 		... and mTOR in responses of ... to BCR and ...   (details)

BCR ➞ MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 17724683

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

European journal of immunology (October 2007)

Abstract

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

BCR-mediated mTOR activation ...   (details)

BCR ➞ MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments
Cause:  BCR   (BCR   CD79A   CD79B )

PMID: 17724683

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

European journal of immunology (October 2007)

Abstract

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

PMID: 21299459
Regulation of mammalian target of rapamycin and mitogen activated protein kinase pathways by BCR-ABL. 		... that BCR-ABL regulates engagement ... of mammalian target of rapamycin (mTOR) and ...   (details)

BCR ➞ MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 21299459

Regulation of mammalian target of rapamycin and mitogen activated protein kinase pathways by BCR-ABL.
Source

Leukemia & lymphoma (February 2011)

Abstract

Regulation of mammalian target of rapamycin and mitogen activated protein kinase pathways by BCR-ABL. A large body of evidence has established that BCR-ABL regulates engagement and activation of mammalian target of rapamycin (mTOR) and mitogen activated protein kinase (MAPK) signaling cascades. mTOR-mediated signals, as well as signals transduced by ERK, JNK, and p38 MAPK, are important components of the aberrant signaling induced by BCR-ABL. Such deregulation of mTOR or MAPK pathways contributes to BCR-ABL leukemogenesis, and their targeting with selective inhibitors provides an approach to enhance antileukemic responses and/or overcome leukemic cell resistance in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). This review explores recent advances in our understanding of mTOR and MAPK signaling in BCR-ABL-expressing leukemias and discusses the potential therapeutic targeting of these pathways in CML and Ph+ ALL.

PMID: 21715304
BCR-ABL suppresses autophagy through ATF5-mediated regulation of mTOR transcription. 		... that BCR-ABL,... stimulates transcription of mammalian target of rapamycin ...   (details)

BCR ➞ MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 21715304

BCR-ABL suppresses autophagy through ATF5-mediated regulation of mTOR transcription.
Source

Blood (9/8/2011)

Abstract

BCR-ABL suppresses autophagy through ATF5-mediated regulation of mTOR transcription. The oncoprotein BCR-ABL transforms myeloid progenitor cells and is responsible for the development of chronic myeloid leukemia (CML). In transformed cells, BCR-ABL suppresses apoptosis as well as autophagy, a catabolic process in which cellular components are degraded by the lysosomal machinery. The mechanism by which BCR-ABL suppresses autophagy is not known. Here we report that in both mouse and human BCR-ABL-transformed cells, activating transcription factor 5 (ATF5), a prosurvival factor, suppresses autophagy but does not affect apoptosis. We find that BCR-ABL, through PI3K/AKT/FOXO4 signaling, transcriptionally up-regulates ATF5 expression and that ATF5, in turn, stimulates transcription of mammalian target of rapamycin (mTOR; also called mechanistic target of rapamycin), a well-established master negative-regulator of autophagy. Previous studies have shown that the BCR-ABL inhibitor imatinib mesylate induces both apoptosis and autophagy, and that the resultant autophagy modulates the efficiency by which imatinib kills BCR-ABL-transformed cells. We demonstrate that imatinib-induced autophagy is because of inhibition of the BCR-ABL/PI3K/AKT/FOXO4/ATF5/mTOR pathway that we have identified in this study.