- Title
- CaMKII kinase activity, targeting and control of cellular functions: effect of single and double phosphorylation of CaMKIIα
- Creator
- Abdul Majeed, A'qilah Banu binte; Pearsall, Elizabeth; Carpenter, Helen; Brzozowski, Joshua; Dickson, Phillip W.; Rostas, John A. P.; Skelding, Kathryn A.
- Relation
- Calcium Signaling Vol. 1, Issue 1, p. 36-51
- Relation
- http://researchpub.org/journal/cs/abstract/vol1-no1.html#paper5
- Publisher
- Research Publisher
- Resource Type
- journal article
- Date
- 2014
- Description
- Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a ubiquitously expressed multifunctional kinase, which regulates many cellular processes, including synaptic plasticity and proliferation. CaMKII is activated by binding calmodulin (CaM), triggered by an increase in intracellular Ca²⁺. CaMKII can autophosphorylate at several residues, including T253, T286, and T305/306, which alters CaMKII activity and targeting in different ways. Phosphorylation at T286 induces autonomous activity, whereas phosphorylation at T305/306 prevents CaMKII activation. Phosphorylation at T253 has no effect on CaMKII activity in vitro. Phosphorylation at each of these sites changes the subcellular location of CaMKII, and alters protein interactions. To investigate the mechanisms by which dual phosphorylation of CaMKII might regulate cellular functions we examined the effects of double phosphomimic mutation (at T253D/T286D or T286D/T305D) on kinase activity and targeting. We showed that both double phosphomimic mutations altered targeting whereas only T286D/T305D altered kinase activity in vitro. We also showed that overexpressing either T253D/T286D or T286D/T305D altered cell proliferation rates, and that this effect was different from the effects observed with the relevant single phosphomimic mutation. These results indicate the importance of targeting as a regulatory mechanism in CaMKII control of cell function.
- Subject
- calcium/calmodulin-stimulated protein kinase II; CaMKII; cell proliferation; kinase activity; protein phosphorylation; protein targeting
- Identifier
- http://hdl.handle.net/1959.13/1061523
- Identifier
- uon:16963
- Identifier
- ISSN:2373-1168
- Language
- eng
- Full Text
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