Signal transduction of constitutively active protein kinase C epsilon

Garczarczyk, Dorota; Totoń, Ewa; Biedermann, Verena; Rosivatz, Erika; Rechfeld, Florian; Rybczyńska, Maria; Hofmann, Johann

doi:10.1016/j.cellsig.2009.01.017

Cited by 26 publications

(31 citation statements)

References 40 publications

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“…This isozyme localization is in agreement with those observed in SH-SY5Y cells (Lanni et al 2004), suggesting that PKCe may be involved in regulating the Golgi-related processes (Lehel et al 1995). Recently, it has been demonstrated that PKCe can induce distinctly different signaling from the Golgi and plasma membrane (Garczarczyk et al 2009). In addition, a direct interaction between PKCe and the Golgi membrane coatomer protein b 0 -COP (RACK2) has been reported (Csukai et al 1997), which was involved in vesicular trafficking (Dorn and Mochly-Rosen 2002).…”

Section: Discussionsupporting

confidence: 87%

Specific subcellular targeting of PKCα and PKCε in normal and tumoral lactotroph cells by PMA-mitogenic stimulus

et al. 2009

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The variations of the intracellular localization of the individual protein kinase C (PKC) isoforms are related with their different biological functions. In this study, we have investigated the precise intracellular translocation of endogenous PKCalpha and PKCepsilon in PMA-stimulated normal and tumoral lactotroph cells by using confocal and immunogold electron microscopy, which was correlated with the rate of cell proliferation of both pituitary cell phenotypes. The present results showed that the short phorbol ester incubation stimulated the proliferation of normal and tumoral lactotroph cells, as determined by the measurement of the BrdU-labelling index. The translocation of PKCalpha to plasma and nuclear membranes induced by PMA was more marked than that observed for PKCepsilon in normal and tumoral lactotroph cells. Our results showed that PKCs translocation to the plasma and nuclear membranes varied from isozyme to isozyme emphasizing that PKCalpha could be related with the mitogenic stimulus exerted by phorbol ester. These data support the notion that specific PKC isozymes may exert spatially defined effects by virtue of their directed translocation to distinct intracellular sites.

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Section: Discussionsupporting

confidence: 87%

Specific subcellular targeting of PKCα and PKCε in normal and tumoral lactotroph cells by PMA-mitogenic stimulus

et al. 2009

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“…In these cells, the epsilon isoform localizes to the Golgi apparatus at steady state, but undergoes nearly complete translocation to the plasma membrane in response to PKC-activating phorbol-esters [15,16]. As expected, we observed that the GFP-PKCε localized to the juxtanuclear Golgi apparatus at steady state when expressed transiently in NIH3T3 cells (Fig.…”

Section: Resultssupporting

confidence: 71%

“…In heart cells, activation of adenosine receptors causes PKCε to redistribute to sarcomeres [8,13,14]. PKCε localizes to the Golgi apparatus in fibroblasts, but rapidly dissociates from the Golgi membrane and translocates to the cell surface or nucleus when PKC-signaling is activated by addition of phorbol esters [10,15-17]. …”

Section: Introductionmentioning

confidence: 99%

ARF1-regulated coatomer directs the steady-state localization of protein kinase C epsilon at the Golgi apparatus

Peterson

Stamnes

2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Protein kinase C epsilon (PKCε) contributes to multiple signaling pathways affecting human disease. The function of PKCε requires it to undergo changes in subcellular distribution in response to signaling events. While the mechanisms underlying this translocation are incompletely understood it involves the receptor for activated C kinase protein (RACK2/β′-COP). This receptor also functions as a vesicle coat protein in the secretory pathway where it is regulated by the small GTP-binding protein ADP-ribosylation factor, ARF1. We inhibited ARF1 activation to test the requirement for RACK2/β′-COP in PKCε localization in NIH3T3 fibroblasts. We found that steady-state localization of PKCε at the Golgi complex requires ARF1-regulated RACK2/β′-COP function. By contrast, we did not observe any defects in phorbol ester-induced translocation when ARF1 was inhibited. We also found that PKCε bound to isolated membranes through two distinct mechanisms. One mechanism was dependent upon RACK2/β′-COP while a second was RACK2/β′-COP-independent and stimulated by phorbol esters. Finally, we show that RACK2/β′-COP affects the subcellular distribution of a constitutively active form of PKCε, in a manner similar to what we observed for wild-type PKCε. Together, our data support a role for RACK2/β′-COP in the steady-state localization of PKCε at the Golgi apparatus, which may be independent of its role during PKCε translocation to the cell surface.

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“…Together, these results indicated that synaptic activity by itself could activate nPKCε to enhance MARCKS phosphorylation at the NMJ and that muscle contraction could be necessary as a mechanism to increase the pnPKCε and pMARCKS levels. It has been described in other synapses and systems a link between phosphorylation of MARCKS and nPKCε [16,45,46]. However, because MARCKS can be phosphorylated by other PKCs we cannot fully discount that isoforms other than nPKCε phosphorylate this PKC-substrate in response to the increased activity, and related to the nPKCε activity, or even that other kinases are involved [47,48].…”

Section: Discussionmentioning

confidence: 96%

The novel protein kinase C epsilon isoform at the adult neuromuscular synapse: location, regulation by synaptic activity-dependent muscle contraction through TrkB signaling and coupling to ACh release

et al. 2015

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BackgroundProtein kinase C (PKC) regulates a variety of neural functions, including neurotransmitter release. Although various PKC isoforms can be expressed at the synaptic sites and specific cell distribution may contribute to their functional diversity, little is known about the isoform-specific functions of PKCs in neuromuscular synapse. The present study is designed to examine the location of the novel isoform nPKCε at the neuromuscular junction (NMJ), their synaptic activity-related expression changes, its regulation by muscle contraction, and their possible involvement in acetylcholine release.ResultsWe use immunohistochemistry and confocal microscopy to demonstrate that the novel isoform nPKCε is exclusively located in the motor nerve terminals of the adult rat NMJ. We also report that electrical stimulation of synaptic inputs to the skeletal muscle significantly increased the amount of nPKCε isoform as well as its phosphorylated form in the synaptic membrane, and muscle contraction is necessary for these nPKCε expression changes. The results also demonstrate that synaptic activity-induced muscle contraction promotes changes in presynaptic nPKCε through the brain-derived neurotrophic factor (BDNF)-mediated tyrosine kinase receptor B (TrkB) signaling. Moreover, nPKCε activity results in phosphorylation of the substrate MARCKS involved in actin cytoskeleton remodeling and related with neurotransmission. Finally, blocking nPKCε with a nPKCε-specific translocation inhibitor peptide (εV1-2) strongly reduces phorbol ester-induced ACh release potentiation, which further indicates that nPKCε is involved in neurotransmission.ConclusionsTogether, these results provide a mechanistic insight into how synaptic activity-induced muscle contraction could regulate the presynaptic action of the nPKCε isoform and suggest that muscle contraction is an important regulatory step in TrkB signaling at the NMJ.

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Signal transduction of constitutively active protein kinase C epsilon

Cited by 26 publications

References 40 publications

Specific subcellular targeting of PKCα and PKCε in normal and tumoral lactotroph cells by PMA-mitogenic stimulus

Specific subcellular targeting of PKCα and PKCε in normal and tumoral lactotroph cells by PMA-mitogenic stimulus

ARF1-regulated coatomer directs the steady-state localization of protein kinase C epsilon at the Golgi apparatus

The novel protein kinase C epsilon isoform at the adult neuromuscular synapse: location, regulation by synaptic activity-dependent muscle contraction through TrkB signaling and coupling to ACh release

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