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RHEBP1 MTOR (1 - 5 of 5)
PMID: 19299511
Specific activation of mTORC1 by Rheb G-protein in vitro involves enhanced recruitment of its substrate protein.
Both Rheb1 and Rheb2 activate mTORC1.   (details)

RHEBP1 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 19299511

Specific activation of mTORC1 by Rheb G-protein in vitro involves enhanced recruitment of its substrate protein.
Source

The Journal of biological chemistry (5/8/2009)

Abstract

Specific activation of mTORC1 by Rheb G-protein in vitro involves enhanced recruitment of its substrate protein. Rheb G-protein plays critical roles in the TSC/Rheb/mTOR signaling pathway by activating mTORC1. The activation of mTORC1 by Rheb can be faithfully reproduced in vitro by using mTORC1 immunoprecipitated by the use of anti-raptor antibody from mammalian cells starved for nutrients. The low in vitro kinase activity against 4E-BP1 of this mTORC1 preparation is dramatically increased by the addition of recombinant Rheb. On the other hand, the addition of Rheb does not activate mTORC2 immunoprecipitated from mammalian cells by the use of anti-rictor antibody. The activation of mTORC1 is specific to Rheb, because other G-proteins such as KRas, RalA/B, and Cdc42 did not activate mTORC1. Both Rheb1 and Rheb2 activate mTORC1. In addition, the activation is dependent on the presence of bound GTP. We also find that the effector domain of Rheb is required for the mTORC1 activation. FKBP38, a recently proposed mediator of Rheb action, appears not to be involved in the Rheb-dependent activation of mTORC1 in vitro, because the preparation of mTORC1 that is devoid of FKBP38 is still activated by Rheb. The addition of Rheb results in a significant increase of binding of the substrate protein 4E-BP1 to mTORC1. PRAS40, a TOR signaling (TOS) motif-containing protein that competes with the binding of 4EBP1 to mTORC1, inhibits Rheb-induced activation of mTORC1. A preparation of mTORC1 that is devoid of raptor is not activated by Rheb. Rheb does not induce autophosphorylation of mTOR. These results suggest that Rheb induces alteration in the binding of 4E-BP1 with mTORC1 to regulate mTORC1 activation.

PMID: 21238928
Rheb1 is required for mTORC1 and myelination in postnatal brain development.
Rheb1 is required for mTORC1 and ...   (details)

RHEBP1 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 21238928

Rheb1 is required for mTORC1 and myelination in postnatal brain development.
Source

Developmental cell (1/18/2011)

Abstract

Rheb1 is required for mTORC1 and myelination in postnatal brain development. mTor kinase is involved in cell growth, proliferation, and differentiation. The roles of mTor activators, Rheb1 and Rheb2, have not been established in vivo. Here, we report that Rheb1, but not Rheb2, is critical for embryonic survival and mTORC1 signaling. Embryonic deletion of Rheb1 in neural progenitor cells abolishes mTORC1 signaling in developing brain and increases mTORC2 signaling. Remarkably, embryonic and early postnatal brain development appears grossly normal in these Rheb1f/f, Nes-cre mice with the notable exception of deficits of myelination. Conditional expression of Rheb1 transgene in neural progenitors increases mTORC1 activity and promotes myelination in the brain. In addition the Rheb1 transgene rescues mTORC1 signaling and hypomyelination in the Rheb1f/f, Nes-cre mice. Our study demonstrates that Rheb1 is essential for mTORC1 signaling and myelination in the brain, and suggests that mTORC1 signaling plays a role in selective cellular adaptations, rather than general cellular viability.

... that Rheb1 is essential for mTORC1 signaling ...   (details)

RHEBP1 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 21238928

Rheb1 is required for mTORC1 and myelination in postnatal brain development.
Source

Developmental cell (1/18/2011)

Abstract

Rheb1 is required for mTORC1 and myelination in postnatal brain development. mTor kinase is involved in cell growth, proliferation, and differentiation. The roles of mTor activators, Rheb1 and Rheb2, have not been established in vivo. Here, we report that Rheb1, but not Rheb2, is critical for embryonic survival and mTORC1 signaling. Embryonic deletion of Rheb1 in neural progenitor cells abolishes mTORC1 signaling in developing brain and increases mTORC2 signaling. Remarkably, embryonic and early postnatal brain development appears grossly normal in these Rheb1f/f, Nes-cre mice with the notable exception of deficits of myelination. Conditional expression of Rheb1 transgene in neural progenitors increases mTORC1 activity and promotes myelination in the brain. In addition the Rheb1 transgene rescues mTORC1 signaling and hypomyelination in the Rheb1f/f, Nes-cre mice. Our study demonstrates that Rheb1 is essential for mTORC1 signaling and myelination in the brain, and suggests that mTORC1 signaling plays a role in selective cellular adaptations, rather than general cellular viability.

PMID: 23567640
Genetic and Pharmacological Inhibition of Rheb1-mTORC1 Signaling Exerts Cardioprotection against Adverse Cardiac Remodeling in Mice.
... that Rheb1 regulates mTORC1 activation ...   (details)

RHEBP1 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 23567640

Genetic and Pharmacological Inhibition of Rheb1-mTORC1 Signaling Exerts Cardioprotection against Adverse Cardiac Remodeling in Mice.
Source

The American journal of pathology (June 2013)

Abstract

Genetic and Pharmacological Inhibition of Rheb1-mTORC1 Signaling Exerts Cardioprotection against Adverse Cardiac Remodeling in Mice. A previous study indicated that Rheb1 is required for mammalian target of TOR complex 1 (mTORC1) signaling in the brain. However, the function of Rheb1 in the heart is still elusive. In the present study, we deleted Rheb1 specifically in cardiomyocytes and found that reduced Rheb1 levels conferred cardioprotection against pathologic remodeling in myocardial infarction (MI) and pressure overload (transverse aortic constriction) mouse models. Cardiomyocyte apoptosis was reduced and mTORC1 activity was suppressed in cardiomyocyte Rheb1-deletion mice, suggesting that Rheb1 regulates mTORC1 activation in myocardium. Furthermore, we demonstrated that astragaloside IV (As-IV) could inhibit mTORC1, and As-IV treatment displayed similar protection against MI and transverse aortic constriction as Rheb1 genetic inhibition. This study indicates that Rheb1 is essential for mTORC1 activation in cardiomyocytes and suggests that targeting Rheb1-mTORC1 signaling, such as by As-IV treatment, may be an effective therapeutic method for treating patients with adverse cardiac remodeling after MI and hypertrophy.

... that Rheb1 is essential for mTORC1 activation ...   (details)

RHEBP1 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 23567640

Genetic and Pharmacological Inhibition of Rheb1-mTORC1 Signaling Exerts Cardioprotection against Adverse Cardiac Remodeling in Mice.
Source

The American journal of pathology (June 2013)

Abstract

Genetic and Pharmacological Inhibition of Rheb1-mTORC1 Signaling Exerts Cardioprotection against Adverse Cardiac Remodeling in Mice. A previous study indicated that Rheb1 is required for mammalian target of TOR complex 1 (mTORC1) signaling in the brain. However, the function of Rheb1 in the heart is still elusive. In the present study, we deleted Rheb1 specifically in cardiomyocytes and found that reduced Rheb1 levels conferred cardioprotection against pathologic remodeling in myocardial infarction (MI) and pressure overload (transverse aortic constriction) mouse models. Cardiomyocyte apoptosis was reduced and mTORC1 activity was suppressed in cardiomyocyte Rheb1-deletion mice, suggesting that Rheb1 regulates mTORC1 activation in myocardium. Furthermore, we demonstrated that astragaloside IV (As-IV) could inhibit mTORC1, and As-IV treatment displayed similar protection against MI and transverse aortic constriction as Rheb1 genetic inhibition. This study indicates that Rheb1 is essential for mTORC1 activation in cardiomyocytes and suggests that targeting Rheb1-mTORC1 signaling, such as by As-IV treatment, may be an effective therapeutic method for treating patients with adverse cardiac remodeling after MI and hypertrophy.