Diversity of the protein kinase C gene family

Harrington, Elizabeth O.; Ware, J. Anthony

doi:10.1016/1050-1738(95)00058-h

Cited by 15 publications

(14 citation statements)

References 54 publications

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“…ANG II has a multitude of intracellular effectors (11). One target of interest is PKC, which is a key regulator of many cellular functions (20). It was hypothesized that if the activation of PKC by ANG II (or by ET-1) mediates the attenuation of the K ϩ currents under investigation, then exposure of cells to a PKC inhibitor would at least partially restore current density.…”

Section: Resultsmentioning

confidence: 99%

“…In these experiments, we used dioctanoyl-rac-glycerol (DiC8), a synthetic analog of diacylglycerol, the endogenous activator of (most isoforms of) PKC (20). The incubation of cells with DiC8 was designed to maintain the activation and translocation of PKC despite the addition of the ACE inhibitor.…”

Section: Resultsmentioning

confidence: 99%

“…The working hypothesis based on these results is that on activation, some of the translocation of PKC-⑀ is to the nucleus. PKC is involved in gene regulation by activation or binding of various transcription factors (20). PKC-⑀ may thus directly suppress the synthesis of channel proteins underlying I peak but only some of the proteins underlying I late .…”

Section: Discussionmentioning

confidence: 99%

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Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Shimoni

Liu

2003

American Journal of Physiology-Heart and Circulatory Physiology

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Shimoni, Yakhin, and Xiu-Fang Liu. Role of PKC in autocrine regulation of rat ventricular K ϩ currents by angiotensin and endothelin. Am J Physiol Heart Circ Physiol 284: H1168-H1181, 2003 10.1152 10. /ajpheart.00748.2002 and sustained K ϩ currents were measured in isolated rat ventricular myocytes obtained from control, steptozotocin-induced (Type 1) diabetic, and hypothyroid rats. Both currents, attenuated by the endocrine abnormalities, were significantly augmented by in vitro incubation (Ͼ6 h) with the angiotensin-converting enzyme inhibitor quinapril or the angiotensin II (ANG II) receptor blocker saralasin. Western blots indicated a parallel increase in Kv4.2 and Kv1.2, channel proteins that underlie the transient and (part of the) sustained currents. Under diabetic and hypothyroid conditions, both currents were also augmented by an endothelin receptor blocker (PD142893) or by an endothelin-converting enzyme inhibitor. Kv4.2 density was also enhanced by PD142893. Incubation (Ͼ5 h) with the PKC inhibitor bisindolylmaleimide augmented both currents, whereas the PKC activator dioctanoyl-rac-glycerol (DiC8) prevented the augmentation of currents by quinapril. DiC8 also prevented the augmentation of Kv4.2 density by quinapril. Specific peptides that activate PKC translocation indicated that PKC-⑀ and not PKC-␦ is involved in ANG II action on these currents. In control myocytes, quinapril and PD142893 augmented the sustained late current but had no effect on peak current. It is concluded that an autocrine release of angiotensin and endothelin in diabetic and hypothyroid conditions attenuates K ϩ currents by suppressing the synthesis of some K ϩ channel proteins, with the effects mediated at least partially by PKC-⑀. diabetes; protein kinase C WE HAVE RECENTLY ESTABLISHED that an autocrine release of angiotensin II (ANG II) plays a central role in attenuating a transient and a sustained K ϩ current in single myocytes isolated from (Type 1) diabetic rats (45). The in vitro blockade of ANG II action or formation (for Ͼ5 h) augments both currents. This effect is blocked by cycloheximide, suggesting that new protein synthesis mediates current augmentation after removal of ANG II-related current inhibition.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Shimoni

Liu

2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…Studies by Thorburn and colleagues (68) suggest that agonist-induced activation of the MAPK pathway is mediated by Raf-1 kinase in cardiac myocytes. Since Raf-1 kinase can be activated by protein kinase C (24, 69 -71), which, in turn, can be activated by products of the PI hydrolysis pathway (72), this could provide a mechanism for activation of the MAPK pathway. However, this mechanism is difficult to reconcile with the results of the present study showing the ␣ 1b -S 288 -294 -AR subtype potently stimulates SRE-luciferase gene expression without any activation of the PI hydrolysis pathway or ANF gene expression.…”

Section: Discussionmentioning

confidence: 99%

Constitutively Active Mutants of the α1a- and the α1b-Adrenergic Receptor Subtypes Reveal Coupling to Different Signaling Pathways and Physiological Responses in Rat Cardiac Myocytes

McWhinney¹,

Wenham²,

Kanwal³

et al. 2000

Journal of Biological Chemistry

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Activation of ␣ 1 -adrenergic receptors influences both the contractile activity and the growth potential of cardiac myocytes. However, the signaling pathways linking activation of specific ␣ 1 -adrenergic receptor (AR) subtypes to these physiological responses remain controversial. In the present study, a molecular approach was used to identify conclusively the signaling pathways activated in response to the individual ␣ 1A -and ␣ 1B -AR subtypes in cardiac myocytes. For this purpose, a mutant ␣ 1a -AR subtype (␣ 1a -S 290/293 -AR) was constructed based on analogy to the previously described constitutively active mutant ␣ 1b -AR subtype (␣ 1b -S 288 -294 -AR). The mutant ␣ 1a -S 290/293 -AR subtype displayed constitutive activity based on four criteria. To introduce the constitutively active ␣ 1 -AR subtypes into cardiac myocytes, recombinant Sindbis viruses encoding either the ␣ 1a -S 290/293 -AR or ␣ 1b -S 288 -294 -AR subtype were used to infect the whole cell population with >90% efficiency, thereby allowing the biochemical activities of the various signaling pathways to be measured. When expressed at comparable levels, the ␣ 1a -S 290/293 -AR subtype exhibited a significantly elevated basal level as well as agonist-stimulated level of inositol phosphate accumulation, coincident with activation of atrial natriuretic factor-luciferase gene expression. By contrast, the ␣ 1b -S 288 -294 -AR subtype displayed a markedly increased serum response element-luciferase gene expression but no activation of atrial natriuretic factor-luciferase gene expression. Taken together, this study provides the first molecular evidence for coupling of the ␣ 1a -AR and the ␣ 1b -AR subtypes to different signaling pathways in cardiac myocytes.Activation of ␣ 1 -adrenergic receptors (AR) 1 influences both the contractile activity and the growth potential of cardiac myocytes. However, despite intense investigation, the signaling pathways linking activation of specific ␣ 1 -AR subtypes to these particular physiological responses remain controversial (1). The situation is complicated by the diversity of ␣ 1 -AR subtypes. Three distinct ␣ 1 -AR subtypes have been identified by molecular cloning (2-4). Recently, the relationships between the cloned and native ␣ 1 -AR subtypes have been established by comparison of their affinity constants for a wide variety of ␣ 1 -AR subtype-selective antagonists (5, 6). From this comparison, it has been suggested that the cloned ␣ 1b -AR represents the native ␣ 1B -AR subtype; the cloned ␣ 1a/c -AR 2 corresponds to the native ␣ 1A -AR subtype; and the cloned ␣ 1d -AR is considered to represent a novel ␣ 1D -AR subtype. With the recognition that multiple ␣ 1 -AR subtypes exist, the roles of the individual ␣ 1 -AR subtypes in mediating specific physiological effects need to be investigated further.The assignment of particular physiological responses and signaling pathways first requires the elucidation of the specific ␣ 1 -ARs subtypes present in cardiac myocytes. In a previous study, we showed that all t...

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“…trophy [3,5,6], ischemia and ischemic preconditioning [7,8], and heart failure [9,10], based on numerous studies Protein kinase C (PKC) is a family of serine / threonine using animal models. kinases which play a major role in signal transduction in It is now recognized that PKC comprises a group of at the heart.…”

Section: Introductionmentioning

confidence: 99%

Molecular heterogeneity of protein kinase C expression in human ventricle

Shin

Barnett

Chang

et al. 2000

Cardiovascular Research

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Objective: Although activation of protein kinase C (PKC) modulates the function of normal cardiac myocytes and likely plays a role in the pathogenesis of cardiomyopathic disease states, the molecular basis of PKC expression in human ventricle has not been examined in detail. Methods: We have performed Western analysis and immunohistochemistry on explanted human cardiac tissue from nondiseased and diseased specimens using isoform-specific antibodies directed against all known PKC isozymes. Results: In homogenates from left and right ventricle, all isoforms except PKC-g and u were detected by immunoblotting, with confirmation using a second antibody directed against a different epitope when possible. For PKC-bII, d, and´, data indicated that these isoforms were variably phosphorylated in vivo, resulting in multiple bands during immunoblotting. Because of potential antibody cross-reactivity, reverse transcriptase polymerase chain reaction (RT-PCR) was performed which confirmed expression of PKC-a, bI, and z. Immunohistochemistry demonstrated that all isoforms detected in ventricular homogenate by Western analysis could be localized to cardiac myocytes. From a methodologic standpoint, significant degradation of PKC isoforms could be demonstrated when samples were either frozen or allowed to remain at room temperature, compared to immediate subcellular fractionation. Conclusions: These findings indicate that the PKC expression in human ventricular myocytes is remarkably diverse, with multiple conventional, novel, and atypical isoforms present, and highlight the importance of sample preparation in comparative studies of PKC isoform expression.

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Diversity of the protein kinase C gene family

Cited by 15 publications

References 54 publications

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Constitutively Active Mutants of the α1a- and the α1b-Adrenergic Receptor Subtypes Reveal Coupling to Different Signaling Pathways and Physiological Responses in Rat Cardiac Myocytes

Molecular heterogeneity of protein kinase C expression in human ventricle

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Diversity of the protein kinase C gene family

Cited by 15 publications

References 54 publications

Role of PKC in autocrine regulation of rat ventricular K+currents by angiotensin and endothelin

Role of PKC in autocrine regulation of rat ventricular K+currents by angiotensin and endothelin

Constitutively Active Mutants of the α1a- and the α1b-Adrenergic Receptor Subtypes Reveal Coupling to Different Signaling Pathways and Physiological Responses in Rat Cardiac Myocytes

Molecular heterogeneity of protein kinase C expression in human ventricle

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Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin