Disease relevance of Camk1

• Using a combination of pharmacological inhibitors and dominant-negative kinases (dnKinase), we identified a requirement for CaMKK acting through CaMKI in the stimulation of ERKs upon depolarization of the neuroblastoma cell line, NG108 [1].

High impact information on Camk1

• We here searched for kinases with a core catalytic structure similar to CaMKI and CaMKIV [2].
• Interestingly, despite a large similarity in the kinase domain, CL1/CL2/CLr had an impact on CRE-dependent gene expression distinct from that of the related CaMKI/CaMKIV and CaMKII [2].
• ERK activation upon depolarization or transfection with constitutively active (ca) CaMKI was blocked by dnRas [1].
• The CaMKI site, Ser(89) ((84)LLRSGSSPNL(93)), fits the expected consensus whereas the CaMKIV site, Ser(24) ((19)SSPALSASAS(28)), is novel [3].
• The multifunctional calcium/calmodulin-dependent protein kinases I and IV (CaMKI and CaMKIV) are closely related by primary sequence and predicted to have similar substrate specificities based on peptide studies [3].

Biological context of Camk1

• We identified a fragment of p300-(1-117) that is a substrate of both kinases, and through both mutagenesis and Edman phosphate ((32)P) release sequencing, established that CaMKI and CaMKIV phosphorylate completely different sites [3].
• Hypertrophy-sensitive reporter activity in primary cardiomyocytes was silenced when tet-inducible CaM KII was co-expressed with plasmids harboring active forms of CaN, CaM KI or CaM KIV [4].
• CaM-KIV as well as CaM-KI are activated upon phosphorylation by two distinct isoforms of Ca2+/calmodulin-dependent protein kinase kinases, CaM-KKs alpha and beta [5].
• In this study, we first examined the developmental gene expression of the four isoforms of CaMKI in mouse brain with special attention to the hippocampal formation by in situ hybridization analysis [6].

Anatomical context of Camk1

• Myocyte exposure to doxycycline (DOX) blocked tTA-driven CaM KII expression and restored CaN/CaM KI or CaN/CaM KIV driven reporter activation [4].
• The overexpression of kinase-dead mutants of CaMKI reduced the average dendritic length of the transfected neurons without any significant effects on the number of primary dendrites and the branching index [6].

Other interactions of Camk1

• However, there are no changes in the levels of CaMKI, which is expressed in the ventricles, or CaMKIV, which is not detectable in the ventricles [7].

References