Therefore, the hyperinsulinemia registered in vivo and in vitro, associated with the impairment of glucose tolerance and the decrease in
AKT phosphorylation, make clear the occurrence of peripheral insulin resistance.
Among the tocotrienols, γ - tocotrienol has also been shown to inhibit
AKT phosphorylation, causing a reduction in NFκB activity induced by carcinogens, growth factors, and several inflammatory stimuli.1 5
ONC201 induced caspase - dependent apoptosis that involved activation of the integrated stress response (ATF4 / CHOP) pathway, inhibition of
Akt phosphorylation, Foxo3a activation, downregulation of cyclin D1, IAP and Bcl - 2 family members.
ActD caused
AKT phosphorylation at Ser473, indicating full activation of AKT.
Measuring the levels of
AKT phosphorylation and FoxO transcriptional activity provide two useful readouts of IIS levels.
Silencing of total mTOR gene expression by siRNA decreased
AKT phosphorylation.
mTOR - rictor complex (composed of mTOR, rictor, and GβL) is not rapamycin sensitive and modulates cell survival and proliferation by direct phosphorylation of AKT on Ser473 and by facilitating
AKT phosphorylation on Thr308 by PDK1 in vitro (13).
Because treatment with rapamycin also led to decreased
AKT phosphorylation in ALK + ALCL cells in our in vitro study, it is tempting to speculate that an effector protein downstream of mTOR - raptor may contribute directly or indirectly to AKT activation.
Akt phosphorylation at pS473 was also measured by ELISA (Thermo Fisher Scientific).
(i, k) Western blot analysis of
AKT phosphorylation (Ser473) in control (shCtr) and Tie2 - silenced (shTie2 I / shTie2 II) BP (i) and HUVEC (k) upon stimulation with rhAng1 or rhAng2.
AKT phosphorylation was Tie2 - dependent as evidenced by shRNA - mediated Tie2 silencing experiments (Fig. 1i — l, Supplementary Fig. 2a, b).
The 0 - nM and 2 - nM insulin treatment conditions were tested, but did not result in measurable
Akt phosphorylation.
In vitro, Pkn1 — / — Cgcs exhibited deregulated axonal outgrowth, elevated
AKT phosphorylation, and higher levels of neuronal differentiation - 2 (NeuroD2), a transcription factor preventing presynaptic maturation.
Not exact matches
Decreased
phosphorylation of PDGFR - ß impairs the angiogenic potential of expanded endothelial progenitor cells via the inhibition of PI3K /
Akt signaling.
Akt - dependent
phosphorylation specifically regulates Cot induction of NF - $ ąppa $ B - dependent transcription.
The enhanced hiPS - HEP cells respond to insulin with
phosphorylation of protein kinase B - α (
Akt), even at low insulin concentrations, and the genes involved in glycogen metabolism, gluconeogenesis, and insulin signaling are expressed at similar levels as in hphep cells.
x
Phosphorylation of Bax Ser184 by
Akt Regulates Its Activity and Apoptosis in Neutrophils.
The effect of insulin on
phosphorylation of
Akt protein was measured by Western blot in enhanced hiPS - HEP cells from C18 on Day 12 post-thawing (n = 3 for the [+] condition; n = 1 for the -LSB----RSB- control).
Here, we show that enhanced hiPS - HEP cells respond to insulin with
phosphorylation of protein kinase B - α (
Akt), even at low insulin concentrations (Figure 4, Panels E and F), and that the genes involved in glycogen metabolism, gluconeogenesis, and insulin signaling are expressed at similar levels as in hphep cells (Figure 4, Panels B, C, and D).
Ang1, but not Ang2, induced
phosphorylation of the Tie2 downstream target
AKT in BP (Fig. 1i, j) as well as in EC (Fig. 1k, l).
AKT activation contributes to mTOR
phosphorylation in ALCL cells.
Recent studies have established that nucleophosmin - ALK mediates oncogenesis, at least in part, through
phosphorylation / activation of the serine / threonine kinase
AKT (4, 5).
We observed that the
phosphorylation level of
AKT significantly correlated with the
phosphorylation level of mTOR and rpS6 as well as with expression of total 4E - BP1 and eIF4E in ALK + ALCL tumors.
Infection of both cell lines with adeno - myrAkt resulted in substantially increased of Ser473p -
AKT levels (A) associated with increased
phosphorylation (activation) of mTOR, p70S6K, and rpS6 (B).
Constitutive activation of
AKT resulted in a substantial increase in the
phosphorylation of mTOR, p70S6K, and rpS6 (Fig. 3A and B).
Of note, treatment of ALCL cell lines with rapamycin also resulted in a slight decrease of Ser473
phosphorylation of
AKT.
Chiang and Abraham (43) have recently shown that mTOR
phosphorylation at Ser2448 is blocked by rapamycin, and this effect is independent of
AKT activation status.
In agreement with this observation, recently Sarbassov et al. (13) have shown that rictor - mTOR (but not mTOR - raptor) complex directly phosphorylates
AKT on Ser473 and facilitates Thr308
phosphorylation by PDK1 in vitro.
However, the PI3K -
AKT - mTOR pathway model seems to be more complex, as recent evidence suggests that rictor - mTOR complex directly phosphorylates
AKT on Ser473 and facilitates Thr308
phosphorylation by PDK1 in vitro and mTOR is directly phosphorylated by p70S6K at Ser2448.
The next slide, a little bit more about Fox01; Fox - 01, as I mentioned, is activated by
Akt through
phosphorylation.
For example, ILPs induce the
phosphorylation of
AKT, which in turn phosphorylates the negative growth regulator Forkhead Box O (FoxO).
Spleen CD4 + T cells were harvested from mice 21 d after transplantation and cultured or not with VPA for 24 h. Western blot assay showed that VPA attenuated the
phosphorylation level of
Akt in a dose - dependent manner (Fig. 4F).
We isolated spleen CD4 + T cells from VPA recipients and vehicle recipients and assessed the
phosphorylation level of
Akt.
(H) Spleen CD4 + T cells harvested from VPA recipients and control mice on day 21 were analyzed by Western blot assay for the expression and
phosphorylation level of
Akt and downstream target proteins.
In this study, we demonstrate that VPA treatment ameliorated GVHD in a mouse BMT model by downregulating Th1 and Th17 cells and reducing inflammatory cytokine levels via inhibition of the
phosphorylation level of
Akt in CD4 + T cells.
The
phosphorylation levels of downstream target proteins of
Akt also were downregulated in parallel (Fig. 4F).
As shown in Fig. 4H, the
phosphorylation levels of
Akt, as well as the downstream target proteins, were reduced in the VPA - treated group compared with vehicle - control group.
Thus, we examined whether VPA treatment could increase the acetylation level of
Akt and, in turn, decrease the
phosphorylation level of
Akt.
Ji H, Ding Z, Hawke D, Xing D, Jiang BH, Mills GB and Lu Z.
AKT - dependent
phosphorylation of Niban regulates nucleophosmin - and MDM2 - mediated p53 stability and cell apoptosis.
In summary, our findings showed that ActD induces the
phosphorylation of
AKT, thereby activating
AKT.
Phosphorylation of
AKT decreased after treatment with ActD for 10 minutes in the 293, 293T, and Hepa - 1c1c7 cells, but still increased after treatment with ActD (10 and 30 nM) for 10 minutes in the HepG2 cells.
Our results showed that ActD induced the
phosphorylation of
AKT at Ser473 within 2 minutes.
Figure 7:
Phosphorylation of
AKT induced by actinomycin D (ActD).
Upon Ser473
phosphorylation by mTORC2,
AKT is fully activated [27].
Induction of autophagy by lithium was matched by increased expression of PTEN (the phosphatase acting on PIP3) and a marked reduction in the SER473
phosphorylation of
Akt (data not shown).