Article

Expanding mTOR signaling

Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Cell Research (Impact Factor: 12.41). 09/2007; 17(8):666-81. DOI: 10.1038/cr.2007.64
Source: PubMed

ABSTRACT

The mammalian target of rapamycin (mTOR) has drawn much attention recently because of its essential role in cell growth control and its involvement in human tumorigenesis. Great endeavors have been made to elucidate the functions and regulation of mTOR in the past decade. The current prevailing view is that mTOR regulates many fundamental biological processes, such as cell growth and survival, by integrating both intracellular and extracellular signals, including growth factors, nutrients, energy levels, and cellular stress. The significance of mTOR has been highlighted most recently by the identification of mTOR-associated proteins. Amazingly, when bound to different proteins, mTOR forms distinctive complexes with very different physiological functions. These findings not only expand the roles that mTOR plays in cells but also further complicate the regulation network. Thus, it is now even more critical that we precisely understand the underlying molecular mechanisms in order to directly guide the development and usage of anti-cancer drugs targeting the mTOR signaling pathway. In this review, we will discuss different mTOR-associated proteins, the regulation of mTOR complexes, and the consequences of mTOR dysregulation under pathophysiological conditions.

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    • "Moreover, mTOR-selective inhibitor rapamycin seems to suppress additive effects of HPEinduced phosphorylation of S6K rather than MTA alone. Because S6K1 is a positive regulator of protein synthesis downstream of mTOR,[41]the mTOR pathway seems to be a master mediator of MTA and HPE-induced odontoblastic differentiation. Collectively, mTOR, MAPK and NF-kB pathways, that are engaged in stimulating growth, differentiation and angiogenesis of HDPCs via MTA and HPE, are schematically drawn based on the current findings, as depicted in Figure 4. "
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