Kinase Isoenzymes and Isoforms

CaM kinase II <1, 3> ( phosphorylates and activates [26] <3> phosphorylation of Thr-311 results in 8-lOfold enzyme activation in the presence of 0.01 mM free Ca " and 0.002 mM calmodulin and in a 25fold increase in sensitivity to the Ca /calmodulin complex [26] <1,3> phosphorylation of isoenzyme B by calmodulin kinase II and protein kinase C added together results in a maximal 60-70fold activation, no effect on the sensitivity to the Ca2 /calmodulin complex, CaM kinase II alone activates 35-40fold in the presence of Ca " and calmodulin [28] <1> endogenous activator of isoform A [30]) [26, 28, 30]... 

Although it is true that abnormal proteins increase with age, most of them are a result of posttranslational changes. An example is the various isoforms of creatine kinase (CK). Here, the major isoenzyme, CK-MM (isoform CK-33), is normally synthesized in the heart and skeletal muscle. However, after its release into the circulation, carboxypeptidase hydrolyzes the terminal lysine from one of the M-peptides to form CK-32. Subsequent hydrolysis of the terminal lysine from the second M-peptide produces the third isoform, CK-3i (W8). Numerous similar posttranslational proteins are produced. Hence, the presence of abnormal proteins per se does not support this aging theory. 

Abendschein DR, Fontanet HL, Nohara R. Optimized preservation of isoforms of creatine kinase MM isoenzyme in plasma specimens and their rapid quantification by semi-automated chromatofocusing. Clin Chem 1990 36 723-7. 

Another consequence of the production of IP3 and DAG is activation of protein kinase C. This serine/ threonine protein kinase occurs in at least 10 different isoenzymic forms. Most of these forms require both bound Ca + and DAG for high enzymic activity. The nature of the substrates of protein kinase C depends both on the isoform and on the tissue(s) in which the isoform is expressed. 

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