Selective Activation of Phospholipase Cγ1 and Distinct Protein Kinase C Subspecies in Intracellular Signaling by Hepatocyte Growth Factor/Scatter Factor in Primary Cultured Rat Neocortical Cells

Machide, Mitsuru; Kamitori, Kazuyo; Nakamura, Yasuko; Kohsaka, Shinichi

doi:10.1046/j.1471-4159.1998.71020592.x

Cited by 28 publications

(22 citation statements)

References 35 publications

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“…In the case of HGF, it has been known to activate PKC in neurons (Machide et al, 1998), and, at the same time, this activation has been demonstrated in ischemia as well as in plasticity. In the ischemic state, there have been many reports showing PKC-mediated phosphorylation and/or activation of the NMDA receptor (Bickler et al, 2004;Cheung et al, 2001;Hammond et al, 1994).…”

Section: Discussionmentioning

confidence: 94%

“…This probably occurs via trafficking of the receptor, since PKCactivation has been reported to transfer NR1/NR2A, a type of NMDA receptor complex that might be dominant in synapses, to the cell surface (Lan et al, 2001). Since HGF is known to activate PKC in neurons (Machide et al, 1998), it is possible that HGF mobilizes NMDA receptor molecules and enhances the current via PKC activation.…”

Section: Discussionmentioning

confidence: 99%

“…Since HGF has been shown to activate PKC in neurons (Machide et al, 1998), we tried to detect PKC-dependent phosphorylation of the NMDA receptor. An antibody for the major phosphorylation sites, Ser896/897, of NR1, an essential subtype of the NMDA receptor, was used for immunoblotting, and the level of phosphorylation was found to be increased in neurons treated with HGF (Fig.…”

Section: Protein Kinase C (Pkc)-dependent Phosphorylation Of the Nmdamentioning

confidence: 99%

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Hepatocyte growth factor as an enhancer of nmda currents and synaptic plasticity in the hippocampus

et al. 2004

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Abstract-Hepatocyte growth factor (HGF) promotes the survival and migration of immature neurons, but its role in the mature brain has remained elusive. In the hippocampus of juvenile rats, we found that the HGF receptor c-Met was expressed in neurons. Furthermore, it was highly Tyrphosphorylated, more so than in the liver under normal conditions, suggesting that the receptor is activated and that HGF may act continuously in the intact brain. Exogenously applied HGF enhanced synaptic long-term potentiation (LTP) in the CA1 region of hippocampus, but did not affect long-term depression. We further found that HGF augmented N-methyl-D-aspartate receptor-mediated currents in both slices and dissociated neurons. This augmentation is likely to underlie the enhancement of LTP. Considering that the expression of both HGF and c-Met are known to be induced by ischemic stimuli, this modulation would provide a novel understanding of a neuronal regulatory systems shared with pathogenic ischemic states.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Protein Kinase C (Pkc)-dependent Phosphorylation Of the Nmdamentioning

confidence: 99%

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Hepatocyte growth factor as an enhancer of nmda currents and synaptic plasticity in the hippocampus

et al. 2004

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“…Members of the PKC family of kinases are major mediators of growth factor signaling. Hepatocyte growth factor stimulation leads to translocation of PKC-a, -e and -g to the inner plasma membrane in neocortical cells thereby activating these isoforms (Machide et al, 1998). Similarly, hepatocyte growth factor can activate PKC-a, -bII, -d and -z in a lung adenocarcinoma line (Awasthi and King, 2000).…”

Section: Egf-dependent Cox-2 Induction Requires Pkc-d K Xu Et Almentioning

confidence: 99%

Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires protein kinase C-δ

Chang

Gao

et al. 2009

Oncogene

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Earlier, we showed that epidermal growth factor receptor (EGFR) signaling in human glioma cells increased cyclooxygenase-2 (COX-2) expression through p38-mitogen-activated protein kinase (MAPK)-dependent activation of the Sp family of transcription factors. Further mechanistic details of EGFR-dependent induction of COX-2 expression in glioma cells remained elusive. Protein kinase Cs (PKCs) comprise a family of serine-threonine kinases that are major mediators of signaling from receptor tyrosine kinases. Here, we report that PKC-d, a novel PKC isoform, plays a role in EGF-dependent COX-2 induction in human glioma cells. Pharmacological inhibition and genetic silencing (through siRNA or dominantnegative expression) of PKC-d confirm a role for this PKC isoform in EGF-dependent COX-2 induction. Overexpression of a functional PKC-d enhanced COX-2 expression indicating that PKC-d is not only necessary but also sufficient to regulate COX-2 levels. Inhibition of p38-MAPK pharmacologically or with siRNA further shows that p38-MAPK is required for activation of PKC-d by EGF while inhibition of PKC-d had no discernible effects on p38-MAPK activation. Finally, EGF stimulation promotes physical interactions between PKC-d and Sp1 resulting in phosphorylation and nuclear localization of this transcription factor. These data provide the first evidence that PKC-d is a critical link between p38-MAPK and Sp1-dependent COX-2 expression in human glioma cells.

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“…This latter DAG production occurs slowly and is more sustained (Shirai et al, 2002) and is induced by growth that activates PLCγ. It had been reported that HGF stimulates PLCγ in neocortical cells and generates DAG (Machide et al 1998). Activation of KGF receptors produces subsequent activation of PLCγ that may increase intracellular levels of DAG culminating with PKC activation (Shaoul et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C alpha and epsilon differentially modulate hepatocyte growth factor-induced epithelial proliferation and migration

Sharma

Kakazu

Bazán

2007

Experimental Eye Research

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Protein kinase C (PKC) isoenzymes require membrane translocation for physiological activation. We have recently shown that the growth factors epidermal growth factor and hepatocyte growth factor (HGF), but not keratinocyte growth factor (KGF), regulate PKCα activation to promote epithelial wound healing (Sharma, G. D., Ottino, P., Bazan, H. E. P., 2005. Epidermal and hepatocyte growth factors, but not keratinocyte growth factor, modulate protein kinase C alpha translocation to the plasma membrane through 15(S)-hydroxyeicosatetraenoic acid synthesis. J. Biol. Chem. 280, 7917-7924).Protein kinase C alpha (PKCα) and protein kinase C epsilon (PKCε) are two differentially regulated isoenzymes. While PKCα requires Ca 2+ for its activation, PKEε is Ca 2+ independent. However, growth factor-induced activation of these enzymes and their specific regulation of epithelial migration and proliferation have not been explored.In the present study, we overexpressed PKCε fused to green fluorescent protein to examine its translocation in real time to the plasma membrane in living human corneal epithelial cells. Stimulation with HGF and KGF demonstrated translocation of PKCε to the plasma membrane.Because HGF activates both PKCs, this growth factor was used to stimulate wound healing. PKCα or PKCε genes were knocked down individually without affecting the basal expression of the other PKC isoform. Gene-knockdown of PKCα significantly inhibited HGF-stimulated proliferation of human corneal epithelial cells. In contrast, PKCε-gene silencing severely impaired the HGFstimulated migratory ability of human corneal epithelial cells. When migrating epithelial cells in the cornea wound bed after injury were transfected with specific PKCα-or PKCε-siRNA, there was a significant delay in wound healing. Corneal wound healing stimulated with HGF in similar conditions was also inhibited. On the other hand, over expression of PKCα or PKCε genes fused with green fluorescent protein in migrating corneal epithelium accelerated repair of the epithelial defect.Our findings demonstrate that PKCα and PKCε modulate different stages of wound healing stimulated by HGF and contribute to epithelial repair by playing selective regulatory roles in epithelial proliferation and migration, both crucial to corneal wound healing.

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Selective Activation of Phospholipase Cγ1 and Distinct Protein Kinase C Subspecies in Intracellular Signaling by Hepatocyte Growth Factor/Scatter Factor in Primary Cultured Rat Neocortical Cells

Cited by 28 publications

References 35 publications

Hepatocyte growth factor as an enhancer of nmda currents and synaptic plasticity in the hippocampus

Hepatocyte growth factor as an enhancer of nmda currents and synaptic plasticity in the hippocampus

Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires protein kinase C-δ

Protein kinase C alpha and epsilon differentially modulate hepatocyte growth factor-induced epithelial proliferation and migration

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