p(FPLX:PKC)
An ever-growing body of evidence indicates that in CNS and parasympathetic nervous system neurons and in heterologous systems expressing specific nAChR subtypes, nicotine stimulates several Ca2+-dependent kinases, including PI3K, protein kinase C (PKC), protein kinase A (PKA), calmodulin-dependent protein kinase II (CAM kinase II), and extracellular signal-regulated kinases (ERKs; Refs. 108, 112, 146, 318, 469). PubMed:19126755
It has been shown that activation of M1 receptors decreases tau hyperphosphorylation via activation of PKC and inhibition of GSK-3β PubMed:26813123
Interestingly, stimulation of M1 mAChR by agonists has been found to enhance sAPPalpha generation and reduce Abeta production[61-70]. Protein kinase C (PKC) is well-known to be activated upon stimulation of M1 mAChR. PKC may promote the activity of alpha-secretase[71] and the traffi cking of APP from the Golgi/ trans-Golgi network to the cell surface PubMed:24590577
When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577
In addition to inhibiting Abeta generation, activation of M1 mAChR counteracts Abeta-induced neurotoxicity through the Wnt signaling pathway, as Abeta impairs the Wnt pathway and M1 mAChR stimulation inactivates GSK-3beta via PKC activation, stabilizes beta-catenin, and induces the expression of Wnt-targeting genes engrailed and cyclin-D1 for neuron survival PubMed:24590577
PMA is a known agonist of PKC, which leads to the activation of the PKC/RAS/RAF/MEK/MAPK pathway that ultimately induces NFkB activation (46–48) PubMed:25331948
Moreover, there is preponderance of data implicating Amyloid-β in the modulation of PKC signaling pathway [335-338] and the PI3K/Akt/mTOR signaling pathway [339-341], which are known to activate NF-κB signaling pathway PubMed:28745240
In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240
ROS activate various downstream signaling molecules, such as PKC and mitogen-activated protein kinases (MAPKs) that induce nuclear translocation of NF-B and the expression of pro-inflammatory genes [41]. PubMed:29179999
Activation of protein kinase C increases APPs α-secretion by mechanisms involving the formation and release of secretory vesicles from the TGN, thus enhancing APP (and possiblyα-secretase) trafficking to the cell surface. PubMed:18650430
Interestingly, PKC can phosphorylate VAChT and regulate its vesicular localization PubMed:26813123
It has been demonstrated that phosphorylation of nicotinic receptors by protein kinase A, protein kinase C, and tyrosine kinase can regulate receptor activity PubMed:26813123
Interestingly, stimulation of M1 mAChR by agonists has been found to enhance sAPPalpha generation and reduce Abeta production[61-70]. Protein kinase C (PKC) is well-known to be activated upon stimulation of M1 mAChR. PKC may promote the activity of alpha-secretase[71] and the traffi cking of APP from the Golgi/ trans-Golgi network to the cell surface PubMed:24590577
Interestingly, stimulation of M1 mAChR by agonists has been found to enhance sAPPalpha generation and reduce Abeta production[61-70]. Protein kinase C (PKC) is well-known to be activated upon stimulation of M1 mAChR. PKC may promote the activity of alpha-secretase[71] and the traffi cking of APP from the Golgi/ trans-Golgi network to the cell surface PubMed:24590577
When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577
In addition to inhibiting Abeta generation, activation of M1 mAChR counteracts Abeta-induced neurotoxicity through the Wnt signaling pathway, as Abeta impairs the Wnt pathway and M1 mAChR stimulation inactivates GSK-3beta via PKC activation, stabilizes beta-catenin, and induces the expression of Wnt-targeting genes engrailed and cyclin-D1 for neuron survival PubMed:24590577
A further potent detaching site is phosphoS214, which can be phosphorylated by PKA and other kinases of the AGC group (PKA/PKG/PKC group of protein kinases), and is up-regulated during mitosis (16, 63). Tau contains one or two cysteines in the repeat domain (C291 in R2, present in 4R isoforms, and C322 in R3), which can be engaged in intra- or intermolecular cross-linking affecting conformation, dimerization and aggregation (108). PubMed:17493042
In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240
The three well characterized sensors of intracellular calcium – calmodulin/CamKII pathway, PI3K/ Akt pathway, and protein kinase C (PKC) pathway – are known to induce NF-κB activation and couple upstream signal transduction pathways that induce calcium dyshomeostasis to NF-κB activation PubMed:28745240
Moreover, there is preponderance of data implicating Amyloid-β in the modulation of PKC signaling pathway [335-338] and the PI3K/Akt/mTOR signaling pathway [339-341], which are known to activate NF-κB signaling pathway PubMed:28745240
In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240
In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240
Several kinase pathways including the calcium-calmodium dependent kinase-II (CaMK), the protein kinases-C (PKC) and the ras/phosphatidylinositol 3-kinase (PI3K) pathways have been implicated in activating neuronal NF-κB signaling PubMed:25652642
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.