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MTOR TSC1 (1 - 2 of 2)
PMID: 12869586
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.
... of TSC1/TSC2 are likely mediated by mTOR.   (details)

MTOR TSC1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 12869586

Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.
Source

Genes & development (8/1/2003)

Abstract

Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2. The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1. These functions of TSC1/TSC2 are likely mediated by mTOR. Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1. This function of Rheb is blocked by rapamycin and dominant-negative mTOR. Rheb stimulates the phosphorylation of mTOR and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status. Our data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth.

PMID: 18177819
Possible mechanisms of disease development in tuberous sclerosis.
... the TSC complex ... direct activation of mammalian target of rapamycin (mTOR) or ...   (details)

MTOR TSC1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 18177819

Possible mechanisms of disease development in tuberous sclerosis.
Source

The lancet oncology (January 2008)

Abstract

Possible mechanisms of disease development in tuberous sclerosis. The two-hit hypothesis presented by Knudson in 1971 explains the development of tumours deficient in anti-oncogenes. Hamartomas in patients with tuberous sclerosis usually fit into this model, the first hit is a congenital lesion of either of the tuberous sclerosis genes (TSC1 or TSC2), and the second hit is loss of heterozygosity of this gene. Although this mechanism is true for most tumours associated with tuberous sclerosis, only 30-60% of brain and cardiac tumours show loss of heterozygosity -- the remaining tumours develop despite the presence of an intact allele. Tumours in which loss of heterozygosity is rare, such as subependymal giant-cell astrocytoma, might all share a common feature that mimics loss of heterozygosity either by inactivation of the TSC complex or by direct activation of mammalian target of rapamycin (mTOR) or its downstream targets. Because phosphorylation of the TSC complex can inactivate it, expression and activation patterns of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK), two potent protein kinases that are activators of the mTOR pathway, have been implicated. AKT activation is detected only in few samples, whereas ERK is hyperactive in all subependymal giant-cell astrocytomas. We postulate that ERK activation consistently detected in different tuberous-sclerosis-associated tumours is a molecular trigger for the development of these neoplasms.