scholarly journals The substrates and binding partners of protein kinase Cε

2010 ◽  
Vol 427 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Philip M. Newton ◽  
Robert O. Messing
Keyword(s):  
Protein Kinase ◽  
Active Drug ◽  
Major Research ◽  
Research Focus ◽  
Cellular Mechanisms ◽  
Future Studies ◽  
Kinase C ◽  
Binding Partners ◽  
Signalling Cascades ◽  
Substrate Phosphorylation

The ε isoform of protein kinase C (PKCε) has important roles in the function of the cardiac, immune and nervous systems. As a result of its diverse actions, PKCε is the target of active drug-discovery programmes. A major research focus is to identify signalling cascades that include PKCε and the substrates that PKCε regulates. In the present review, we identify and discuss those proteins that have been conclusively shown to be direct substrates of PKCε by the best currently available means. We will also describe binding partners that anchor PKCε near its substrates. We review the consequences of substrate phosphorylation and discuss cellular mechanisms by which target specificity is achieved. We begin with a brief overview of the biology of PKCε and methods for substrate identification, and proceed with a discussion of substrate categories to identify common themes that emerge and how these may be used to guide future studies.

Reactive oxygen-mediated contraction in pulmonary arterial smooth muscle: cellular mechanisms

1991 ◽  
Vol 69 (3) ◽  
pp. 383-388 ◽  
Author(s):  
N. Jin ◽  
C. S. Packer ◽  
R. A. Rhoades
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cellular Mechanisms ◽  
Kinase C ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle ◽  
Oxidase Reaction

Reactive oxygen species (at least relatively high doses) cause contraction of pulmonary arterial smooth muscle. The objective of the present study was to elucidate the possible cellular mechanisms involved in reactive oxygen-mediated contraction. Isolated arterial rings from Sprague–Dawley rats were placed in tissue baths containing Earle's balanced salt solution. The maximum active force production (Po) in response to 80 mM KCl was obtained. All other responses were normalized as percentages of Po for comparative purposes. Exposure to reactive oxygen (generated from either the xanthine oxidase reaction (XO) or the glucose oxidase reaction) resulted in pulmonary arterial muscle developing mean active tension of 17.1 ± 3.0% Po. This contraction was independent of extracellular calcium, since it was not affected by verapamil (a calcium channel blocker) or by placement of the arterial muscle in calcium-free media. Phentolamine (an α1-receptor blocker) and propranolol (a β-receptor blocker) did not diminish the response to XO. Ryanodine (a SR calcium release inhibitor), while reducing the response to norepinephrine, did not affect the response to XO. However, H-7 (an inhibitor of protein kinase C) decreased the XO-mediated contraction by 49%. These results indicate that while Ca2+ may not be involved as a second messenger, protein kinase C activity appears to play a role in the transduction pathway of reactive oxygen species mediated contraction of pulmonary arterial smooth muscle.Key words: muscle calcium, α1-receptor, ryanodine, protein kinase C, vascular smooth muscle, oxygen radicals, verapamil.

scholarly journals Decoding of Short-lived Ca2+Influx Signals into Long Term Substrate Phosphorylation through Activation of Two Distinct Classes of Protein Kinase C

2003 ◽  
Vol 278 (11) ◽  
pp. 9896-9904 ◽  
Author(s):  
Hideo Mogami ◽  
Hui Zhang ◽  
Yuko Suzuki ◽  
Tetsumei Urano ◽  
Naoaki Saito ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase C ◽  
Substrate Phosphorylation

scholarly journals Protein kinase C-δ regulates the subcellular localization of Shc in H2O2-treated cardiomyocytes

2010 ◽  
Vol 299 (4) ◽  
pp. C770-C778 ◽  
Author(s):  
Jianfen Guo ◽  
Lin Cong ◽  
Vitalyi O. Rybin ◽  
Zoya Gertsberg ◽  
Susan F. Steinberg
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Stress Responses ◽  
Growth Regulation ◽  
Adapter Proteins ◽  
Kinase C ◽  
Binding Partners ◽  
Mitochondrial Fractions ◽  
Subcellular Compartmentalization ◽  
Oxidative Stress Responses

Protein kinase C-δ (PKCδ) exerts important cardiac actions as a lipid-regulated kinase. There is limited evidence that PKCδ also might exert an additional kinase-independent action as a regulator of the subcellular compartmentalization of binding partners such as Shc (Src homologous and collagen), a family of adapter proteins that play key roles in growth regulation and oxidative stress responses. This study shows that native PKCδ forms complexes with endogenous Shc proteins in H2O2-treated cardiomyocytes; H2O2 treatment also leads to the accumulation of PKCδ and Shc in a detergent-insoluble cytoskeletal fraction and in mitochondria. H2O2-dependent recruitment of Shc isoforms to cytoskeletal and mitochondrial fractions is amplified by wild-type-PKCδ overexpression, consistent with the notion that PKCδ acts as a signal-regulated scaffold to anchor Shc in specific subcellular compartments. However, overexpression studies with kinase-dead (KD)-PKCδ-K376R (an ATP-binding mutant of PKCδ that lacks catalytic activity) are less informative, since KD-PKCδ-K376R aberrantly localizes as a constitutively tyrosine-phosphorylated enzyme to detergent-insoluble and mitochondrial fractions of resting cardiomyocytes; relatively little KD-PKCδ-K376R remains in the cytosolic fraction. The aberrant localization and tyrosine phosphorylation patterns for KD-PKCδ-K376R do not phenocopy the properties of native PKCδ, even in cells chronically treated with GF109203X to inhibit PKCδ activity. Hence, while KD-PKCδ-K376R overexpression increases Shc localization to the detergent-insoluble and mitochondrial fractions, the significance of these results is uncertain. Our studies suggest that experiments using KD-PKCδ-K376R overexpression as a strategy to competitively inhibit the kinase-dependent actions of native PKCδ or to expose the kinase-independent scaffolding functions of PKCδ should be interpreted with caution.

1,25-Dihydroxyvitamin D3Enhances Phorbol Ester-Stimulated Differentiation and Protein Kinase C-Dependent Substrate Phosphorylation Activity in the U937 Human Monoblastoid Cell

Endocrinology ◽  
1987 ◽  
Vol 121 (5) ◽  
pp. 1654-1661 ◽  
Author(s):  
D. KIRK WAYS ◽  
RICHARD C. DODD ◽  
THOMAS E. BENNETT ◽  
T. KENNEY GRAY ◽  
H. SHELTON EARP
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Kinase C ◽  
Substrate Phosphorylation

Short-term regulation of renal Na-K-ATPase activity: physiological relevance and cellular mechanisms

1993 ◽  
Vol 265 (6) ◽  
pp. F743-F755 ◽  
Author(s):  
A. M. Bertorello ◽  
A. I. Katz
Keyword(s):  
Protein Kinase ◽  
Atpase Activity ◽  
Renal Tubules ◽  
Short Term ◽  
Cellular Mechanisms ◽  
Sodium Potassium ◽  
Kinase C ◽  
Physiological Relevance ◽  
Intracellular Messengers ◽  
Intracellular Signal

Sodium-potassium-activated adenosinetriphosphatase (Na-K-ATPase; the Na:K pump), located at the basolateral domain of epithelial cells, provides the driving force for active sodium and potassium translocation and for the secondary active transport of other solutes across the renal tubules. Short-term regulation of renal Na-K-ATPase activity (i.e., not reflecting changes in its biosynthesis rate) provides an important mechanism of modulating tubule transport and thus the final Na and K urinary excretion. Recent studies have provided abundant evidence that such regulation is effected by complex functional networks that are specific for different nephron segments and involve distinct and often mutually interacting intracellular signal transduction pathways. The effects of hormones and autacoids linked to alterations in cell adenosine 3',5'-cyclic monophosphate and consequently of protein kinase A, in the levels and distribution of protein kinase C, or in the generation of various eicosanoids provide examples of rapid Na:K pump activity modulation by the mechanisms mentioned above. In this review we assess the roles of specific intracellular messengers and the manner in which they, and especially protein kinases, might interact with the pump in the short-term regulation of its activity; also, we examine the emerging evidence supporting the participation of the cytoskeleton in this process.

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