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Calmodulin-Dependent Protein Kinase (CaM Kinase) Inhibitors

 

Many effects of Ca2+ are mediated by Ca2+/calmodulin(CaM)- dependent protein kinases (CaM kinases). CaM kinases constitute a family of structurally related enzymes that include phosphorylase kinase, myosin light chain kinase, and CaM kinases I-IV. CaM kinase II, one of the best-studied multifunctional enzymes, is found in high concentrations in neuronal synapses, and in some regions of the brain it may constitute up to 2% of the total protein content. Activation of CaM kinase II has been linked to memory and learning processes in the vertebrate nervous system. CaM kinase II is a complex of about 12 subunits that exist in four differentially expressed forms (a, b, g, and d). The a and b isoforms are most abundant in neurons, whereas d or g isoforms are expressed in most tissues. The d isoform is the most prominent isoform in cardiomyocytes. In the inactive state there is a strong interaction between the inhibitory and catalytic domains of the enzyme. The binding of Ca2+/CaM allows the catalytic domain to phosphorylate the inhibitory domain. Once activated, CaM kinase II retains significant activity even after the withdrawal of Ca2+, thereby prolonging the duration of kinase activity. Several synthetic and naturally occurring compounds have been shown to bind CaM in a Ca2+-dependent manner and block the activation of CaM-dependent enzymes. These compounds have been extensively used in investigating the mechanism of Ca2+-binding and activation in biological systems.

Merck:/topic/images/Biosciences/ISB/CaM-Kinase.jpgReferences:
Cai, H., et al. 2008. Cardiovasc. Res. 77, 30.
Griffith, L.C. 2004. J. Neurosci. 24, 8391.
Fujisawa, H. 2000. J. Biochem. (Tokyo) 129, 193.
Rokolya, A., and Singer, H.A. 2000. Am. J. Physiol. 278, C537.
Fukunaga, K., and Miyamoto, E. 1999. Jap. J. Pharmacol. 79, 7.
Kemp, B.E., et al. 1994. In Protein Kinases (Woodgett, J.R., ed.), Oxford Univ. Press, N.Y. pp 30-67.

Products in this category:
Catalog number Products
208710 [Ala286]-Ca2+/Calmodulin Kinase II Inhibitor 281-301 
189480 Autocamtide-2 Related Inhibitory Peptide - Calbiochem 
189484 Autocamtide-2 Related Inhibitory Peptide II - Calbiochem 
189485 Autocamtide-2 Related Inhibitory Peptide II, Cell-permeable - Calbiochem 
189482 Autocamtide-2 Related Inhibitory Peptide, Myristoylated - Calbiochem 
208711 Ca2+/Calmodulin Kinase II Inhibitor 281-309 - Calbiochem 
208734 Calmodulin Binding Domain - CAS 115044-69-4 - Calbiochem 
208920 Calmodulin Kinase IINtide - Calbiochem 
208921 Calmodulin Kinase IINtide, Myristoylated - Calbiochem 
208922 CaMKII Inhibitor, CK59 - CAS 140651-18-9 - Calbiochem 
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