RESEARCH ARTICLE In vitro substrate phospho 2+ e 0

has been classified as a novel member of the calmodulin bers including the catalytic subunit of AMPK (AMPKα) at Thr172 [5-8] and SAD-B (known as a brain-specific kinase, Yurimoto et al. BMC Biochemistry 2012, 13:27 http://www.biomedcentral.com/1471-2091/13/27malian CaMKK isoforms bind to Ca2+/CaM as well as toScience and Technology, Okayama University, 3-1-1, Tsushima-naka, Kita-ku, Okayama 700-8530, Japankinase (CaMK) family that specifically phosphorylates a single Thr residue (Thr177 or Thr196, respectively) within the activation loop in each of two multifunctional cal-modulin (CaM) kinases, CaMKI and CaMKIV; these phos-phorylation events cause a large increase in catalytic efficiency [1-3]. Accumulated biochemical evidence indi-cates that CaMKK phosphorylates Akt/Protein kinase B [4] BRSK1) at Thr189 [9]; either phosphorylation event causes significant catalytic activation, and these findings indicate that CaMKK confers Ca2+ dependence on other signalling pathways. In mammals, two CaMKK genes (CaMKKα and CaMKKβ) have been identified, and both are highly expressed in the brain; the α isoform is also expressed in various peripheral tissues such as thymus and spleen [10]. A CaMKK gene has been found in Caenorhabditis elegans and in Aspergillus nidulans, and the proteins encoded by these genes are components of the CaMK cascade within the respective organisms [11,12]. Interestingly, both mam