Localization, Anchoring, and Functions of Protein Kinase C Isozymes in the Heart

Mackay, Katrina; Mochly‐Rosen, Daria

doi:10.1006/jmcc.2001.1400

Cited by 131 publications

(90 citation statements)

References 53 publications

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“…Although specific cellular adaptor proteins that mediate differential membrane localization and activities of the two PKCs have been reported (16,75,83,84), our present study implies that distinct membrane binding and activation mechanisms of these PKCs might also contribute to their differential cellular actions. Our previous study showed that PKC⑀ has little PS specificity and has generally lower affinity than PKC␣ for any anionic vesicles (e.g.…”

Section: Discussionmentioning

confidence: 53%

Mechanism of Diacylglycerol-induced Membrane Targeting and Activation of Protein Kinase Cδ

Stahelin

Digman

Medkova³

et al. 2004

Journal of Biological Chemistry

121

155

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The regulatory domains of novel protein kinases C (PKC) contain two C1 domains (C1A and C1B), which have been identified as the interaction site for sn-1,2-diacylglycerol (DAG) and phorbol ester, and a C2 domain that may be involved in interaction with lipids and/or proteins. Although recent reports have indicated that C1A and C1B domains of conventional PKCs play different roles in their DAG-mediated membrane binding and activation, the individual roles of C1A and C1B domains in the DAG-mediated activation of novel PKCs have not been fully understood. In this study, we determined the roles of C1A and C1B domains of PKC␦ by means of in vitro lipid binding analyses and cellular protein translocation measurements. Isothermal titration calorimetry and surface plasmon resonance measurements showed that isolated C1A and C1B domains of PKC␦ have opposite affinities for DAG and phorbol ester; i.e. the C1A domain with high affinity for DAG and the C1B domain with high affinity for phorbol ester. Furthermore, in vitro activity and membrane binding analyses of PKC␦ mutants showed that the C1A domain is critical for the DAG-induced membrane binding and activation of PKC␦. The studies also indicated that an anionic residue, Glu 177 , in the C1A domain plays a key role in controlling the DAG accessibility of the conformationally restricted C1A domain in a phosphatidylserine-dependent manner. Cell studies with enhanced green fluorescent protein-tagged PKC␦ and mutants showed that because of its phosphatidylserine specificity PKC␦ preferentially translocated to the plasma membrane under the conditions in which DAG is randomly distributed among intracellular membranes of HEK293 cells. Collectively, these results provide new insight into the differential roles of C1 domains in the DAG-induced membrane activation of PKC␦ and the origin of its specific subcellular localization in response to DAG.

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Section: Discussionmentioning

confidence: 53%

Mechanism of Diacylglycerol-induced Membrane Targeting and Activation of Protein Kinase Cδ

Stahelin

Digman

Medkova³

et al. 2004

Journal of Biological Chemistry

121

155

View full text Add to dashboard Cite

show abstract

“…PKC comprises a large family of serine-threonine kinases and plays an important role in the regulation of cardiovascular functions. The documented 12 members of the PKC family are classified according to their structure and substrate requirements (24,36,37). In this study, using PKC isoform-selective inhibitors, we show that PKC-␣/␤1 play a critical role in the regulation of MMP-9 expression and activity, whereas activation of PKC-and PKC-plays a critical role in the regulation of expression and activity of MMP-2 and -9.…”

Section: Discussionmentioning

confidence: 69%

Differential Regulation of Matrix Metalloproteinase-2 and -9 Expression and Activity in Adult Rat Cardiac Fibroblasts in Response to Interleukin-1β

Xie

Singh

2004

Journal of Biological Chemistry

139

120

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“…37 Dempsey et al 38 found that cardiac myocytes contain at least six different PKC isozymes but preconditioning results in activation of only two isozymes, PKC-d and PKC-e. Quantitation of PKC-isoform expression showed the dominance of the Ca 2+ -dependent PKCa over PKC-d and PKC-e. PKC-a is the single isozyme that translocates to the contractile system on Ca 2+ stimulation in the rat heart, suggesting a unique physiological role for PKCa in the Ca 2+ -dependent regulation of myofibrillar contractility. 39,40 The a-subunit of Gq is a well-established mediator of hypertrophic growth in neonatal cardiomyocytes and in mouse hearts. Studies have found that although aortic AR-a 1A , AR-a 1B and AR-a 1D are associated with Gqa, AR-a 1B is also linked to Goa and the couple AR-a 1B -Goa mediates the contractile response of rat aorta.…”

Section: Discussionmentioning

confidence: 99%

Is overall blockade superior to selective blockade of adrenergic receptor subtypes in suppressing left ventricular remodeling in spontaneously hypertensive rats?

et al. 2010

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To test the hypothesis that nonselective blockade of adrenergic receptor (AR) subtypes is superior to selective blockade of AR subtypes in suppressing left ventricular (LV) remodeling induced by hypertension. Sixty-four spontaneously hypertensive rats (SHR) were randomly divided into four groups: bisoprolol-treated, propranolol-treated, carvedilol-treated and no treatment groups (n¼16, each). Sixteen Wistar-Kyoto (WKY) rats served as a control group. Echocardiography and cardiac catheterization were carried out to record the mitral flow velocity ratio of E wave to A wave (E/A), LV mass index (LVMI), maximal rising (dp/dt max ) and falling (Àdp/dt max ) rate of the LV pressure and LV relaxation time constant (s). The mRNA and protein expression levels of AR, protein kinase(PK) and G-protein subtypes, intracellular free calcium (Ca 2+ ) concentration and cardiocyte apoptoisis rate were determined. Three drug-treated groups showed higher velocity ratio of E wave to A wave (E/A) and Àdp/dt max and lower systolic blood pressure (SBP), LVMI, s, apoptosis rate and intracellular free Ca 2+ concentration than the no treatment group. The mRNA expression levels of AR-a 1B in the carvedilol group were significantly lower than the other two drug-treated groups. The mRNA expression levels of AR-b 1 , AR-b 2 and Gsa were significantly higher in the three drug-treated groups than in the no treatment group, with the expression levels of AR-b 2 being the highest in the carvedilol-treated group. The protein expression levels of PKA and PKC subtype a and d were lower in the three drug-treated groups than in the no treatment group. Overall blockade of AR subtypes is not superior to selective blockade of AR subtypes in suppressing LV remodeling in SHR. Although carvedilol is the most effective in attenuating cardiocyte apoptosis, normalizing AR-a 1B and Gsa expression and increasing AR-b 2 expression.

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Localization, Anchoring, and Functions of Protein Kinase C Isozymes in the Heart

Cited by 131 publications

References 53 publications

Mechanism of Diacylglycerol-induced Membrane Targeting and Activation of Protein Kinase Cδ

Mechanism of Diacylglycerol-induced Membrane Targeting and Activation of Protein Kinase Cδ

Differential Regulation of Matrix Metalloproteinase-2 and -9 Expression and Activity in Adult Rat Cardiac Fibroblasts in Response to Interleukin-1β

Is overall blockade superior to selective blockade of adrenergic receptor subtypes in suppressing left ventricular remodeling in spontaneously hypertensive rats?

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