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phosphoinositide-3-kinase-related kinase (PIKK) family, was identified soon
after.
26-29
It was later discovered that mTOR associates with the regulatory
associated protein of mTOR (raptor)
30
and mammalian counterpart of yeast
Lst8 (MLST8) (also known as G protein b-subunit-like protein, GbL)
31
in a
protein complex now referred to as mTOR complex 1 (mTORC1; see Figure
14.2). The central role of mTOR and its complexes in cell signaling (particularly
in the context of cancer) has been reviewed extensively.
32
In addition, mTOR
also exists in a second protein complex, mTORC2, consisting of mTOR,
MLST8 (GbL), stress-activated protein kinase-interacting protein (sin1), and
rapamycin-insensitive companion of mTOR (rictor),
33
but not raptor. As
the name implies, this complex is not inhibited by rapamycin, except under
Figure 14.2
The protein kinase B-mammalian target of rapamycin signaling path-
way. 4E-BP, eIF-4E-binding protein; Akt, protein kinase B; IGF-R,
insulin-like growth factor receptor; IRS1, insulin receptor substrate 1;
mLST8, mammalian counterpart of yeast Lst8; mTORC, mammalian
target of rapamycin complex; PDK, phosphoinositol-dependent protein
kinase; PI3K, phosphatidylinositol 3-kinase; PIP2, phosphatidylinositol
(4,5)-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate;
PRAS-40, proline-rich Akt substrate of 40 kDa; PTEN, phosphatase and
tensin homolog deleted on chromosome 10; REDD1, regulated in
development and DNA damage responses; S6K, p70 S6 kinase; SIN1,
stress-activated protein kinase interaction protein 1; TSC, tuberous
sclerosis. Reproduced with permission from R.T. Abraham and C. H.
Eng, Exp. Opin. Ther. Targets, 2008, 12, 209-222.
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