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Demonstration of a Ca2+/calmodulin dependent protein kinase cascade in the hog heart
A Uemura1, Y Naito, T Matsubara
1Department of Pharmacology, Third Department of Internal Medicine, Nagoya University School of Medicine, Tsurumai 65, Showa-ku, Nagoya, 466-8550, Japan.
Insights
Researchers identified novel cardiac Ca2+ signal transduction components, discovering CaMKI and CaMK kinase (CaMKK) in hog hearts. This reveals a heart-specific CaMK cascade, crucial for understanding cardiac function.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- Ca2+/calmodulin dependent protein kinase (CaMK) family and cascades are well-characterized in the brain.
- Limited information exists regarding cardiac CaMK equivalents, with only CaMKII previously reported in the heart.
Purpose of the Study:
- To identify and characterize CaMKI and its activator, CaMK kinase (CaMKK), in the hog heart.
- To investigate the existence of a heart-specific CaMK cascade.
Main Methods:
- Purification and characterization of CaMKI and CaMKK from hog heart.
- Analysis of CaMKI phosphorylation activity on cardiac phospholamban peptide.
- Assessment of CaMKI autophosphorylation dependence on CaMKK.
Main Results:
- CaMKI was identified as the alpha isoform (41 kDa), capable of phosphorylating cardiac phospholamban peptide and undergoing CaMKK-dependent autophosphorylation.
- CaMKK was identified as a 67 kDa band, distinct from its brain counterpart.
- These findings suggest a heart-specific CaMK cascade involving CaMKI and CaMKK.
Conclusions:
- A novel heart-specific CaMK cascade, comprising CaMKI and CaMKK alongside CaMKII, has been identified.
- This cascade plays a significant role in cardiac Ca2+ signal transduction.
- Further consideration of this pathway is essential for understanding cardiac physiology and pathology.
Abstract:
Members of the Ca2+/calmodulin dependent protein kinase (CaMK) family and a CaMK cascade have been identified and well characterized in the brain, but little is known about their equivalents in the heart. Thus only CaMKII and its function have been reported so far. Therefore, we purified and characterized CaMKI and CaMK kinase (CaMKK) as an associated activator from the hog heart for the first time. The heart CaMKI was revealed to be the alpha isoform of brain CaMKI with a molecular weight of 41 kDa to phosphorylate cardiac phospholamban peptide, and to exhibit autophosphorylation requiring CaMKK. Heart CaMKK was found as a 67 kDa band and proved to be a different kinase from that in brain. These data indicate the existence of a heart specific CaMK cascade, consisting of CaMKI and CaMKK, along with CaMKII, which should be taken into account in any consideration of Ca2+ signal transduction.