Protein Kinase C (PKC) Activity Regulates Functional Effects of Kvβ1.3 Subunit on KV1.5 Channels

David, Miren; Macías, Álvaro; Moreno, Cristina; Prieto, Angela; Martínez-Mármol, Ramón; Vicente, Rubén; González, Teresa; Felipe, Antônio; Tamkun, Michael M.; Valenzuela, Carmen

doi:10.1074/jbc.m111.328278

Cited by 19 publications

(20 citation statements)

References 61 publications

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“…References PKCs myofibrillar myosin light chain-2 (MLC2v; rat Ser15) modulation of force generation [166] titin (PEVK region; Ser11878, Ser12022) modulation of titin compliance [167] muscle lim protein (MLP, CSRP3) modulation of PKC activity [42] muscle ankyrin repeat proteins (Ankrd1/CARP1, Thr11, Thr116, Ser305; Ankrd2/CARP2; Ankrd23/ CARP3) unknown, potential regulation of stretch-responsive signaling pathways [168] troponin-I (Ser42, Ser44, Ser76, Ser198, Thr143, Ser198) modulation of force generation [169][170][171][172][173][174][175] troponin-T (Ser1, Thr194, Ser198, Thr203 and Thr284, Ser179) myosin binding protein-C (MyBPC, Ser275, Ser302, Ser304) modulation of force generation [69,166] ion channels & pumps, membrane-associated proteins L-type calcium channel Ca(v)1.2 (α1C-subunit, Ser1674, Ser1928) increased channel activity [59,176] Connexin-43 (Cx43, Ser368) regulation of subcellular Cx43 distribution [177] K(v)1.5 channel (Kvβ1.3 regulatory subunit) modulation of channel activity [70] ryanodine receptor (RyR) modulation of channel activity [178] sarcoendoplasmic reticulum Ca 2+ -ATPase (SERCA) modulation of SERCA activity [179] phospholamban (PLN, Ser16, Ser10?) modulation of SERCA activity, unknown roles for Ser10 phosphorylation [60,61] vinculin (Ser1033, Ser1045) modulation of lipid-docking [180] signaling β2-adrenergic receptor (β2-AR; Ser261, Ser262, Ser344, Ser345) modulation of adrenergic signaling & force generation [181] G-protein coupled receptor kinase (GRK2, Ser29; GRK5) enhances GRK activity, modulation of adrenergic signaling [182,183] histone deacetylase 5 (HDAC5; Ser259, Ser498) modulation of nuclear shuttling and transcriptional activity [34,184] signal transducer and activator of transcription 3 (STAT3, Ser727?)…”

Section: Cardiac Rolesmentioning

confidence: 99%

“…Studies investigating novel PKCs in the heart have largely focused on their role during ischemia-reperfusion injury, centering on molecular functions in mitochondria. However, novel PKC isozymes have also been shown to be able to phosphorylate substrates outside mitochondria, including myosin-binding protein-C (MyBPC) or the regulatory subunit of the voltage gated potassium channel (Kv1.5) [69,70].…”

Section: Novel Pkcsmentioning

confidence: 99%

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PKC and PKN in heart disease

Marrocco

Bogomolovas

Ehler³

et al. 2019

Journal of Molecular and Cellular Cardiology

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The protein kinase C (PKC) and closely related protein kinase N (PKN) families of serine/threonine protein kinases play crucial cellular roles. Both kinases belong to the AGC subfamily of protein kinases that also include the cAMP dependent protein kinase (PKA), protein kinase B (PKB/AKT), protein kinase G (PKG) and the ribosomal protein S6 kinase (S6K). Involvement of PKC family members in heart disease has been well documented over the years, as their activity and levels are mis-regulated in several pathological heart conditions, such as ischemia, diabetic cardiomyopathy, as well as hypertrophic or dilated cardiomyopathy. This review focuses on the regulation of PKCs and PKNs in different pathological heart conditions and on the influences that PKC/PKN activation has on several physiological processes. In addition, we discuss mechanisms by which PKCs and the closely related PKNs are activated and turned-off in hearts, how they regulate cardiac specific downstream targets and pathways, and how their inhibition by small molecules is explored as new therapeutic target to treat cardiomyopathies and heart failure.

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Section: Cardiac Rolesmentioning

confidence: 99%

Section: Novel Pkcsmentioning

confidence: 99%

PKC and PKN in heart disease

Marrocco

Bogomolovas

Ehler³

et al. 2019

Journal of Molecular and Cellular Cardiology

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“…Several studies have revealed that protein kinase C (PKC) modify the current kinetics of Kv1.5 through phosphorylation of either Kvb1.2 13,14 or Kvb1.3. 15,16 Furthermore, it has been reported that SGK1 upregulates Kv1.5 current through a downregulation of the neural precursor cell expressed developmentally downregulated protein 4-2 (Nedd4-2), which is an E3 type ubiquitin ligase. 17 …”

Section: Introductionmentioning

confidence: 99%

PKC and AMPK regulation of Kv1.5 potassium channels

et al. 2015

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“…Block of Kv1.5 channels by n −3 and n −6 PUFAs resembles the effects of open-channel blockers and Kvβ1.3 regulatory subunits (Snyders et al, 1992; Valenzuela et al, 1995; Yeola et al, 1996; Franqueza et al, 1997; Gonzalez et al, 2002b; Decher et al, 2005, 2008; Arias et al, 2007; David et al, 2012). However, although these open-channel blockers interact with the inner part of the ion pore (Yeola et al, 1996; Franqueza et al, 1997; Decher et al, 2004), the PUFAs blockade appeared to be the consequence of their interaction with an external binding site in the channel.…”

Section: Effects Of N−3 Pufas On the Gating Of Kv15 Channelsmentioning

confidence: 99%

Polyunsaturated Fatty Acids Modify the Gating of Kv Channels

Moreno¹,

Macías²,

Prieto³

et al. 2012

Front. Pharmacol.

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Polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which are attributed to their capability to modulate ion channels. This PUFAs ability has been reported to be due to their effects on the gating properties of ion channels. In the present review, we will focus on the role of PUFAs on the gating of two Kv channels, Kv1.5 and Kv11.1. Kv1.5 channels are blocked by n−3 PUFAs of marine [docosahexaenoic acid (DHA) and eicosapentaenoic acid] and plant origin (alpha-linolenic acid, ALA) at physiological concentrations. The blockade of Kv1.5 channels by PUFAs steeply increased in the range of membrane potentials coinciding with those of Kv1.5 channel activation, suggesting that PUFAs-channel binding may derive a significant fraction of its voltage sensitivity through the coupling to channel gating. A similar shift in the activation voltage was noted for the effects of n–6 arachidonic acid (AA) and DHA on Kv1.1, Kv1.2, and Kv11.1 channels. PUFAs-Kv1.5 channel interaction is time-dependent, producing a fast decay of the current upon depolarization. Thus, Kv1.5 channel opening is a prerequisite for the PUFA-channel interaction. Similar to the Kv1.5 channels, the blockade of Kv11.1 channels by AA and DHA steeply increased in the range of membrane potentials that coincided with the range of Kv11.1 channel activation, suggesting that the PUFAs-Kv channel interactions are also coupled to channel gating. Furthermore, AA regulates the inactivation process in other Kv channels, introducing a fast voltage-dependent inactivation in non-inactivating Kv channels. These results have been explained within the framework that AA closes voltage-dependent potassium channels by inducing conformational changes in the selectivity filter, suggesting that Kv channel gating is lipid dependent.

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Protein Kinase C (PKC) Activity Regulates Functional Effects of Kvβ1.3 Subunit on KV1.5 Channels

Cited by 19 publications

References 61 publications

PKC and PKN in heart disease

PKC and PKN in heart disease

PKC and AMPK regulation of Kv1.5 potassium channels

Polyunsaturated Fatty Acids Modify the Gating of Kv Channels

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