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Acta Physiologica 2007; Volume 189, Supplement 653
The 86th Annual Meeting of The German Physiological Society
3/25/2007-3/28/2007
Hannover, Germany
TRANSREGULATION OF KINETICS OF CALCIUM CALMODULIN KINASE II (CAMKII) IS IMPLICATED IN ANTI-APOPTOTIC CONTROL
Abstract number: O20-5
Fahrmann1 M, Honisch1 S, Kaufhold1 MA, Leitges1 M, Beil1 W
1Medizinische Hochschule Hannover, Institut fr Pharmakologie
Application of PP1/PP2B inhibitors revealed implication of CaMKII in apoptosis. Physiological relevance and mechanism of CaMKII-triggered apoptosis, however, remains largely unclear. Here we suggest that stringent tuning of activity regulating phosphorylations of CaMKII at T286/287 and T305/306 protects cells from long-term hyperactivity and, therefore, increased rate of apoptosis. Calcium-induced kinetics of tubulovesicular CaMKII showed a rapid but transient increase of hyperphosphorylation at T286/287 and T305/306 which reached a peak after 7 min. Hyperphosphorylation was rapidly followed by a half lower but constant level of phosphorylation designated adaptation. Disturbance of CaMKII transregulation by the PP1/PP2A-inhibitor calyculin A resulted in long-term (>20 min) hyperphosphorylation of T286/287 as well as T305/306, and strongly correlated with an increased rate of apoptosis. Adaptation of phosphorylation at T286/287 failed if phosphatases PP1, PP2A, PP2B or PKC-a were either pharmacologically blocked, or, in the case of PKC-a, were knocked out in mice. In contrast, secretory membrane-associated, autonomous CaMKII was, remarkably robust towards regulations by PP1, PP2A, PP2B or PKC-a. In conclusion, if adaptation failed CaMKII became long-term hyperactive for more than 20 min which seemed to be sufficient to trigger apoptosis.
To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 189, Supplement 653 :O20-5