Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.11.17 extracted from

  • Fischer, T.H.; Herting, J.; Tirilomis, T.; Renner, A.; Neef, S.; Toischer, K.; Ellenberger, D.; Foerster, A.; Schmitto, J.D.; Gummert, J.; Schoendube, F.A.; Hasenfuss, G.; Maier, L.S.; Sossalla, S.
    Ca2+/calmodulin-dependent protein kinase II and protein kinase A differentially regulate sarcoplasmic reticulum Ca2+ leak in human cardiac pathology (2013), Circulation, 128, 970-981.
    View publication on PubMed

Application

Application Comment Organism
medicine CaMKII inhibition may be a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
autocamide-2-related inhibitory peptide i.e. AIP, used in its myristoylated form Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
sarcoplasmic reticulum
-
Homo sapiens 16529
-

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ required Homo sapiens
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + ryanodine receptor type 2 Homo sapiens i.e. RyR2 ADP + phosphorylated ryanodine receptor type 2
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
heart Left ventricular myocardial tissue Homo sapiens
-
myocardium
-
Homo sapiens
-
myocyte
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + ryanodine receptor type 2 i.e. RyR2 Homo sapiens ADP + phosphorylated ryanodine receptor type 2
-
?

Synonyms

Synonyms Comment Organism
Ca2+/calmodulin-dependent protein kinase II
-
Homo sapiens
CaMKII
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
assay at room temperature Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens
Calmodulin required Homo sapiens

General Information

General Information Comment Organism
metabolism in human hypertrophy, both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca2+ leak. In the transition from hypertrophy to heart failure, the diastolic Ca2+ leak increases and disturbed Ca2+ cycling occurs. This is associated with an increase in CaMKII- but not PKA-dependent RyR2 phosphorylation. PKA-dependent RyR2 phosphorylation is not increased in heart failure and is independent of previous beta-blocker treatment. In heart failure, CaMKII inhibition but not inhibition of PKA yields a reduction of the SR Ca2+ leak. PKA inhibition further reduced SR Ca2+ load and systolic Ca2+ transients. CaMKII inhibition may thus reflect a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction Homo sapiens
physiological function In hypertrophy, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA) both phosphorylated RyR2 at levels that were not different from healthy myocardium. In heart failure, the sarcoplasmic reticulum Ca2+ leak is nearly doubled compared with hypertrophy, which leads to reduced systolic Ca2+ transients, a depletion of sarcoplasmic reticulum Ca2+ storage and elevated diastolic Ca2+ levels. This is accompanied by a significantly increased CaMKII-dependent phosphorylation of RyR2. In heart failure, CaMKII inhibition but not inhibition of PKA yields a reduction of the sarcoplasmic reticulum Ca2+ leak Homo sapiens