Phosphorylation of calf thymus H1 histone by calcium-activated, phospholipid-dependent protein kinase

Iwasa, Yasushi; Takai, Yoshimi; Kikkawa, Ushio; Nishizuka, Yasutomi

doi:10.1016/0006-291x(80)91198-5

Cited by 74 publications

(25 citation statements)

References 23 publications

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“…It is established that PKC phosphorylates PLN and that the phosphorylation via PKC is additive to that via PKA and CaMKII, but the significance of these findings and the mechanisms involved remain poorly understood (39)(40)(41). It has been suggested that EPAC mediates a novel pathway of regulatory crosstalk between the cAMP and the PLC/PKC pathways (42), and so we hypothesized that EPAC mediates PLN phosphorylation on serine-16 via PLC/PKC.…”

Section: Epac-selective Camp Analogue Increases Pln Phosphorylation Omentioning

confidence: 99%

Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses

Okumura¹,

Fujita²,

Cai³

et al. 2014

J. Clin. Invest.

148

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PKA phosphorylates multiple molecules involved in calcium (Ca 2+ ) handling in cardiac myocytes and is considered to be the predominant regulator of β-adrenergic receptor-mediated enhancement of cardiac contractility; however, recent identification of exchange protein activated by cAMP (EPAC), which is independently activated by cAMP, has challenged this paradigm. Mice lacking Epac1 (Epac1 KO) exhibited decreased cardiac contractility with reduced phospholamban (PLN) phosphorylation at serine-16, the major PKA-mediated phosphorylation site. In Epac1 KO mice, intracellular Ca 2+ storage and the magnitude of Ca 2+ movement were decreased; however, PKA expression remained unchanged, and activation of PKA with isoproterenol improved cardiac contractility. In contrast, direct activation of EPAC in cardiomyocytes led to increased PLN phosphorylation at serine-16, which was dependent on PLC and PKCε. Importantly, Epac1 deletion protected the heart from various stresses, while Epac2 deletion was not protective. Compared with WT mice, aortic banding induced a similar degree of cardiac hypertrophy in Epac1 KO; however, lack of Epac1 prevented subsequent cardiac dysfunction as a result of decreased cardiac myocyte apoptosis and fibrosis. Similarly, Epac1 KO animals showed resistance to isoproterenol-and aging-induced cardiomyopathy and attenuation of arrhythmogenic activity. These data support Epac1 as an important regulator of PKA-independent PLN phosphorylation and indicate that Epac1 regulates cardiac responsiveness to various stresses.

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Section: Epac-selective Camp Analogue Increases Pln Phosphorylation Omentioning

confidence: 99%

Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses

Okumura¹,

Fujita²,

Cai³

et al. 2014

J. Clin. Invest.

148

View full text Add to dashboard Cite

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“…It has been suggested that PKC may play a role in Ca extrusion into the cytosol immediately after its mobilization, and that Catransport ATPase is a possible target of this protein kinase. Studies with myocardial sarcoplasmic reticulum suggest that Ca-transport ATPase is activated by the application of PKC (14). In our experiments, we studied whether the specific inhibition of PKC activity by calphostin C would affect ischemia/reperfusion-induced injury in our model system.…”

Section: Back To Top Discussionmentioning

confidence: 99%

The Role of Protein Kinase C in Ischemic/Reperfused Preconditioned Isolated Rat Hearts

Tósaki

Maulik

Engelman

et al. 1996

Journal of Cardiovascular Pharmacology

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Summary: Protein kinase C (PKC) has been implicated in the preconditioning-induced cardiac protection in ischemic/reperfused myocardium. We studied the effect of PKC inhibition with calphostin C (25, 50, 100, 200, 400, and 800 nM), a potent and specific inhibitor of PKC, in isolated working nonpreconditioned and preconditioned ischemic/reperfused hearts. In the nonpreconditioned groups, all hearts underwent 30 min of nonmothermic global ischemia followed by 30 min of reperfusion. In the preconditioned groups, hearts were subjected to four cycles of ischemic preconditioning by using 5 min of ischemia followed by 10 min reperfusion, before the induction of 30 min ischemia and reperfusion. At low concentrations of calphostin C (25, 50, and 100 nM), the PKC inhibitor had no effect on the incidence of arrhythmias or postischemic cardiac function in the nonpreconditioned ischemic/reperfused groups. With 200 and 400 nM of calphostin C, a significant increase in postischemic function and a reduction in the incidence of arrhythmias were observed in the nonpreconditioned ischemic/reperfused groups. Increasing the concentration of calphostin C to 800 nM, the recovery of postischemic cardiac function was similar to that of the drug-free control group. In preconditioned hearts, lower concentrations (<100 nM) of calphostin C did not change the response of the myocardium to ischemia and reperfusion in comparison to the preconditioned drug-free myocardium. Two hundred and 400 nM of the PKC inhibitor further reduced the incidence of ventricular fibrillation (VF) from the preconditioned drug-free value of 50% to 0 (p < 0.05) and 0 (p < 0.05), respectively, indicating that the combination of the two, preconditioning and calphostin C, affords significant additional protection. Increasing the concentration of calphostin C to 800 nM blocked the cardioprotective effect of preconditioning (100% incidence of VF). The recovery of cardiac function was similarly improved at calphostin C doses of 200 and 400 nM and was reduced at 800 nM (p < 0.05). With 200 and 400 nM of calphostin C, both cytosolic and particulate PKC activity were reduced by [almost equal to]40 and 60%, respectively, in both preconditioned and

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“…reported as a major substrate for protein kinase C in chick hearts, 39 and an A/ r =46,000 protein is among those phosphorylated by protein kinase C in canine cardiac sarcolemma. 40 The function of pp42 in the heart is unknown.…”

Section: Platelets Platelets + Myocytesmentioning

confidence: 97%

Angiotensin II-induced protein phosphorylation in the hypertrophic heart of the Dahl rat.

Sunga

Rabkin

1992

Hypertension

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Angiotensin II-induced phosphorylation of proteins was examined in isolated myocytes from hearts of Dahl rats. A high salt diet induced cardiac hypertrophy in Dahl salt-sensitive rats. Angiotensin H-induced phosphorylation of a 42-kd protein (pp42) was detected by two-dimensional electrophoresis in hypertrophic but not normal ventricular myocytes. Angiotensin II stimulation was time-dependent, with a peak effect at 30 minutes. The half-maximal and maxima] concentrations of angiotensin II that stimulated pp42 phosphorylation were 1 and 10 nM, respectively. Phosphorylation of pp42 was a function of cardiac hypertrophy. Phorbol 12-myristate 13-acetate-induced phosphorylation of pp42 indicates the possibility of an association between protein kinase C and the signal transduction pathway of angiotensin II-induced pp42 phosphorylation. Ionomycin and A23187 (both at 1 /iM) did not stimulate phosphorylation of pp42. Angiotensin II produced a small increase in the synthesis of myocyte proteins in both normal and hypertrophic cells as shown by ["S]methionine incorporation. However, this increase could not account for the increase in the phosphate content of pp42. This protein was not an isofonn of actin nor was it of platelet origin. These results raise the possibility that angiotensin II may play a role in the activation of factors in hypertrophic myocytes; however, further study is required to define a link between phosphorylation of pp42 and the hypertrophic process.

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Phosphorylation of calf thymus H1 histone by calcium-activated, phospholipid-dependent protein kinase

Cited by 74 publications

References 23 publications

Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses

Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses

The Role of Protein Kinase C in Ischemic/Reperfused Preconditioned Isolated Rat Hearts

Angiotensin II-induced protein phosphorylation in the hypertrophic heart of the Dahl rat.

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