Calmodulin-dependent protein kinase kinases CaMKK

AMPK can also be activated by a Ca2+-mediated pathway involving phosphorylation at Thr-172 by the Ca2+/calmodulin-dependent protein kinase, CaMKK 3. CaMKKa and CaMKK 3 were discovered as the upstream kinase for the calmodulin-dependent protein kinases-1 and -IV they both activate AMPK in a Ca2+/ calmodulin-dependent manner in cell-free assays, although CaMKK 3 appears to much more active against AMPK in intact cells. Expression of CaMKKa and CaMKK(3 primarily occurs in neural tissues, but CaMKKp is also expressed in some other cell types. Thus, the Ca2+-mediated pathway for AMPK activation has now been shown to occur in response to depolarization in rat neuronal tissue, in response to thrombin (acting via a Gq-coupled receptor) in endothelial cells, and in response to activation of the T cell receptor in T cells. 

Calmodulin dependent Kinases. Calmodulin-dependent kinases further relay and amplify the calcium signal from calmodulin to their target proteins. In animals, the identified calmodulin-dependent kinases include CaM-dependent kinase kinase (CaMKK), CaM kinase I-IV (CaMKI-IV), in which CaMKII is also known as elongation factor-2 kinase (eEF 2K), MLCKs and so on. CaMKK, CaMKI, CaMKII, and CaMKIV have multiple targets that involve them in multiple activities, while eEF-2K and MLCK have much more restricted targets. CaMKK is at the upstream of the CaMKI and CaMKIV kinase cascade. CaMKK activates CaMKI and CaMKIV through the phosphorylation of these two kinases. The other substrate for CaMKK is protein kinase B (PKB). The activity of CaMKK itself is inhibited by protein... 

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