Protein Kinase C Phosphorylation of Cardiac Troponin I and Troponin T Inhibits Ca2+-Stimulated MgATPase Activity in Reconstituted Actomyosin and Isolated Myofibrils, and Decreases Actin-Myosin Interactions

Noland, Thomas A.; Kuo, J.F.

doi:10.1006/jmcc.1993.1007

Cited by 76 publications

(44 citation statements)

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“…19 Noland and Kuo 19 showed that exclusive phosphorylation of cTnT results in ϳ60% decrease in maximum MgATPase activity in fully reconstituted systems. When cTnI was exclusively phosphorylated under the same conditions, only ϳ20% decrease was observed, suggesting that cTnT phosphorylation is important in regulating cardiac contractility.…”

Section: Discussionmentioning

confidence: 99%

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ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes

Liu

Sharma

et al. 2003

The American Journal of Pathology

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There is increasing support for the idea that excessive production of proinflammatory mediators such as tumor necrosis factor (TNF) and reactive oxygen species (ROS) contribute to the pathogenesis of cardiac dysfunction. However, the mechanisms by which cytokine/ROS production mediates cardiac dysfunction have not been established. Given that apoptosis signal-regulating kinase 1 (ASK1) is highly expressed in cardiac muscle and that ASK1 is an important mediator in the signaling pathways induced by tumor necrosis factor, interleukin-1, and ROS, we used the yeast two-hybrid system with ASK1 as bait to identify ASK1 substrates from a human heart cDNA library. The cDNA encoding the cardiac troponin T (cTnT) was isolated. ASK1 specifically interacted with cTnT, but not cTnI, in vitro and in vivo via the C-terminal ASK1 domain. ASK1 specifically phosphorylated cTnT in vitro and in vivo. Mutations in cTnT (T194/S198) at an ASK1-phosphorylation consensus sequence significantly reduced phosphorylation by ASK1. ROS-induced ASK1 activation, cTnT phosphorylation, and contractile dysfunction in cardiomyocytes showed similar kinetics. Moreover, overexpression of constitutively active ASK1 induces cTnT phosphorylation and inhibits shortening and calcium transient in adult cardiomyocytes. We conclude that ASK1 plays an important role in regulation of cardiac contractile function by phosphorylating cTnT and may participate in cytokine/ROS-induced pathogenesis of cardiomyopathy and heart failure.

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Section: Discussionmentioning

confidence: 99%

“…Phosphorylation of myofilament proteins (including cTnT and cTnI) is important in the regulation of contractile activity. 16,19,36 We examined if association of ASK1 with cTnT results in phosphorylation of cTnT. First we examined phosphorylation of cTnT by ASK1 in vitro.…”

Section: Ask1 Phosphorylates Ctnt At T194 and S198mentioning

confidence: 99%

ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes

Liu

Sharma

et al. 2003

The American Journal of Pathology

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“…Although cTnI and cTnT are the most probable PKC substrates (130)(131)(132)(133), it is not established clearly whether their phosphorylation takes place in in vivo conditions. Nonetheless, PKC-mediated phosphorylation of cTnI and cTnT has been reported to have negative effects on myofibrillar function, such as inhibition of maximal MgATPase activity, and to decrease myofilament Ca 2+ sensitivity, maximal tension development and crossbridge cycling kinetics, depending on the experimental conditions (131)(132)(133)(134)(135)(136). It should also be noted that some PKC isoforms may cross-phosphorylate the PKA phosphorylation sites on cTnI (132,137), which can in turn modify the PKCspecific effects.…”

Section: Myofibrillar Assembly In Congestive Hfmentioning

confidence: 99%

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

Macháčková¹,

Barta²,

Dhalla³

2006

Canadian Journal of Cardiology

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“…I or TN . T by protein kinase C inhibits the ATPase activity of reconstituted actomyosin or myofibrils without affecting the Ca2+ sensitivity [39]. Although we have not checked on the state of phosphorylation of TN .…”

Section: Discussionmentioning

confidence: 90%

Ca²⁺ Binding to Cardiac Troponin C in the Myofilament Lattice and Its Relation to the Myofibrillar ATPase Activity

Morimoto

Ohtsuki

1994

European Journal of Biochemistry

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The Ca2+‐binding properties of troponin C in the intact myofilament lattice and their relation to the activation of ATPase were investigated with isolated porcine cardiac myofibrils. Ca2+ binding, which is composed of two classes of binding sites with different affinities (classes 1 and 2), was clearly detected by a novel method for subtracting the large background activity of myofibrillar Ca2+ binding. The classes 1 and 2 were equivalent stoichiometrically to the two high‐affinity sites (sites III and IV) and a single low‐affinity site (site II) of troponin C. In the presence of ATP, positive cooperativity was observed in the Ca2+ binding of class‐2 sites and the Hill equation parameters were in excellent agreement with those for the Ca2+‐activated myofibrillar ATPase activity, which indicated that the activation of ATPase is a linear function of the Ca2+ occupancy of site II. In the absence of ATP, a marked increase in the affinity of only class‐2 sites was observed while the cooperativity was lost. These results provide direct evidence that some feedback mechanism exists between myosin crossbridge attachment and the Ca2+ binding to site II of troponin C, which may thus confer positive cooperativity on the Ca2+ activation of myofibrillar ATPase activity.

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Protein Kinase C Phosphorylation of Cardiac Troponin I and Troponin T Inhibits Ca2+-Stimulated MgATPase Activity in Reconstituted Actomyosin and Isolated Myofibrils, and Decreases Actin-Myosin Interactions

Cited by 76 publications

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ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes

ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

Ca²⁺ Binding to Cardiac Troponin C in the Myofilament Lattice and Its Relation to the Myofibrillar ATPase Activity

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Protein Kinase C Phosphorylation of Cardiac Troponin I and Troponin T Inhibits Ca2+-Stimulated MgATPase Activity in Reconstituted Actomyosin and Isolated Myofibrils, and Decreases Actin-Myosin Interactions

Cited by 76 publications

References 0 publications

ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes

ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

Ca2+ Binding to Cardiac Troponin C in the Myofilament Lattice and Its Relation to the Myofibrillar ATPase Activity

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Ca²⁺ Binding to Cardiac Troponin C in the Myofilament Lattice and Its Relation to the Myofibrillar ATPase Activity