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2014 ; 36
(ä): 79-90
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Growing knowledge of the mTOR signaling network
#MMPMID25242279
Huang K
; Fingar DC
Semin Cell Dev Biol
2014[Dec]; 36
(ä): 79-90
PMID25242279
show ga
The kinase mTOR (mechanistic target of rapamycin) integrates diverse
environmental signals and translates these cues into appropriate cellular
responses. mTOR forms the catalytic core of at least two functionally distinct
signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1
promotes anabolic cellular metabolism in response to growth factors, nutrients,
and energy and functions as a master controller of cell growth. While
significantly less well understood than mTORC1, mTORC2 responds to growth factors
and controls cell metabolism, cell survival, and the organization of the actin
cytoskeleton. mTOR plays critical roles in cellular processes related to
tumorigenesis, metabolism, immune function, and aging. Consequently, aberrant
mTOR signaling contributes to myriad disease states, and physicians employ mTORC1
inhibitors (rapamycin and analogs) for several pathological conditions. The
clinical utility of mTOR inhibition underscores the important role of mTOR in
organismal physiology. Here we review our growing knowledge of cellular mTOR
regulation by diverse upstream signals (e.g. growth factors; amino acids; energy)
and how mTORC1 integrates these signals to effect appropriate downstream
signaling, with a greater emphasis on mTORC1 over mTORC2. We highlight dynamic
subcellular localization of mTORC1 and associated factors as an important
mechanism for control of mTORC1 activity and function. We will cover major
cellular functions controlled by mTORC1 broadly. While significant advances have
been made in the last decade regarding the regulation and function of mTOR within
complex cell signaling networks, many important findings remain to be discovered.