Disease relevance of Camkk1

• The purified CaM-kinase IV kinase phosphorylated and concomitantly activated CaM-kinase IV purified from rat brain as well as the recombinant kinase expressed in Escherichia coli in a Ca2+/calmodulin-dependent manner [1].

High impact information on Camkk1

• Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway [2].
• RT-PCR, Western blotting, and immunohistochemical staining analysis revealed that CaM-K kinase-alpha (CaM-KKalpha) and CaM-KIV were localized in rat pancreatic beta-cells and their cell line, INS-1 [3].
• By using catalytic chimera and point mutants of both isoforms, we demonstrated that Val(269) in CaM-KK beta/Leu(233) in CaM-KK alpha confers a distinct sensitivity ( approximately 10-fold) to STO-609 on CaM-KK isoforms [4].
• Here we report the activation of CaMKIV, which is phosphorylated by CaMK kinase and localized predominantly in neuronal nuclei, and its functional role as a cyclic AMP-responsive element-binding protein (CREB) kinase in high frequency stimulation (HFS)-induced LTP in the rat hippocampal CA1 region [5].
• In this study, we identify a CaM-KK from Caenorhabditis elegans, and comparison of its sequence with the mammalian CaM-KK alpha and beta shows a unique Arg-Pro (RP)-rich insert in their catalytic domains relative to other protein kinases [6].

Biological context of Camkk1

• Calmodulin-dependent protein kinase IV (CaM-kinase IV), which plays crucial roles in the functioning of Ca2+ in the central nervous system and immune system, is markedly activated upon phosphorylation by the action of CaM-kinase IV kinase [7].
• These data indicate the existence of a heart specific CaMK cascade, consisting of CaMKI and CaMKK, along with CaMKII, which should be taken into account in any consideration of Ca2+ signal transduction [8].
• These observations suggest that CaM-kinase IV may undergo a posttranslational modification, probably Ca2+/calmodulin-dependent phosphorylation by CaM-kinase IV kinase, before exhibiting activity in the central nervous system [9].
• Treatment of neurons with 1,8-naphthoylene benzimidazole-3-carboxylic acid (STO-609), an inhibitor of CaMKK, causes a similar change in morphology and reduction in growth cone motility, and this inhibition can be rescued by transfection with an STO-609-insensitive mutant of CaMKK or by transfection with constitutively active CaMKI [10].
• The CaMKK gene is localized to human chromosome 12 [11].

Anatomical context of Camkk1

• We provided a rabbit antiserum against 20 amino acid residues at the carboxyl-terminal end of CaM-kinase IV kinase, and examined regional and intracellular distribution of CaM-kinase IV kinase immunohistochemically in the central nervous system of the rat by light and electron microscopy [12].
• In the present study, CaM-kinase kinase beta, distinct from Cam-kinase kinase alpha which had been purified and cloned from rat cerebral cortex, was purified approximately 5,000-fold from rat cerebellum and its properties were examined [13].
• These results identify CaMKI as a positive transducer of growth cone motility and axon outgrowth and provide a new physiological role for the CaMKK-CaMKI pathway [10].

Associations of Camkk1 with chemical compounds

• The phosphorylation of CaM-kinase IV by CaM-kinase IV kinase occurred on only serine residue(s) [1].

Enzymatic interactions of Camkk1

• Present study revealed that CaMKK also phosphorylated CaM kinase IV associated with the activation of its activity [14].

Regulatory relationships of Camkk1

• Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV) is activated by CaM-kinase IV kinase [12].

Other interactions of Camkk1

• In vitro kinase assay has demonstrated the marked enhancement of the Ca2+/CaM-dependent activity of CaMKI gamma 1 by the preincubation with Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), but no significant activation of CaMKI gamma 2 [15].
• Ca2+/calmodulin-dependent protein kinase (CaM kinase) I and IV are thought to be activated by CaM kinase kinases (CaMKK) [16].
• In the present study, CaM-kinase IV kinase was purified approximately 2,000-fold from rat cerebral cortex by purification procedures including calmodulin affinity chromatography, and its properties were examined [1].

Analytical, diagnostic and therapeutic context of Camkk1

• The purified CaM-kinase kinase beta gave a doublet at positions corresponding to molecular weights of 66,000 to 67,000 on SDS-PAGE, and neither protein band reacted with antibody against CaM-kinase kinase alpha [13].
• Northern and Western blot analyses of CaM-kinase IV kinase showed relatively weak reactions in the rat cerebellum, where the activity of CaM-kinase IV kinase has been demonstrated to exist, indicating that CaM-kinase IV kinase isoforms distinct from the enzyme cloned from the cerebral cortex may exist in the cerebellum [7].
• A human cDNA clone encoding the calcium/calmodulin-dependent protein kinase kinase (CaMKK) was isolated by RT-PCR amplification of the fragment corresponding to the conserved kinase catalytic domain followed by rapid amplification of cDNA ends and cDNA library screening [11].

References