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metabolism. For example, PKB has been shown to induce the localization of
hexokinases to mitochondria, a process that can directly couple glucose metab-
olism to oxidative phosphorylation via yet-to-be defined mediator(s) (
Gottlob
et al., 2001
). As a wide range of cellular physiology is mediated by PKB, it is
not unexpected that dysregulation of PKB as well as its kinase mTORC2 are
found to be involved in a variety of pathological conditions including cancers
and diabetes (
Hers et al., 2011
;
Oh and Jacinto, 2011
). PKB has been localized
to the BTB and apical ES in the seminiferous epithelium of rat testes, and its
expression at these sites was found to be stage-specific, being highest at stage
VI-VII but considerably diminished by early stageVIII and further diminished
by late stageVIII of the epithelial cycle when BTB restructuring and apical ES
degeneration take place to facilitate preleptotene spermatocyte migration and
spermiation at the corresponding site (
Siu et al., 2005
). It is noted that this pat-
tern of stage-specific expression of PKB at the apical ES is somewhat similar
to the stage-specific expression of p-rpS6 at the apical ES (
Mok et al., 2012c
),
illustrating PKB and rpS6 can be the downstream signaling molecules and
substrates of mTORC2 and mTORC1, respectively, that mediate cross talk
between the two mTOR signaling complexes.
3.3.2.2. Protein Kinase C-
α
Unlike the other two mTORC2 effectors PKB and SGK1, which are sub-
strates of mTORC2, it remains unclear whether PKC-α is directly phos-
phorylated by mTORC2 or through other mediator(s) (
Sarbassov et al.,
2004
). However, after the knockdown of rictor by RNAi, phosphorylation
of PKC-α on S657 was shown to be reduced, resulting in the change of cell
shape due to actin reorganization in which actin filaments at the cortical sides
became less prominent and stress fibers were formed in the cytosol. Similar
morphology of actin cytoskeleton was observed after PKC-α knockdown,
validating actin organization is indeed regulated by mTORC2 and is medi-
ated through PKC-α (
Sarbassov et al., 2004
). In addition to that, a recent
study showed that RNAi-mediated knockdown of rictor in cultured Sertoli
cells also led to a reduced PKC-α phosphorylation, which in turn resulted
in actin reorganization (
Mok et al., 2012a
). Furthermore, addition of serum
to serum-starved fibroblasts induced rapid and robust stress-fiber formation,
which was ablated by a knockdown of mTORC2 subunits mTOR, mLST8
and rictor (
Jacinto et al., 2004
). Furthermore, during the actin cytoskeleton
restructuring due to the knockdown of mTORC2 subunits, a decline in
GTP-bound Rac1 was observed. Whereas cells overexpressing constitutively
active form of Rac1 and Rho were able to resist actin reorganization due to
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