Cellular Signaling through Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II

Calcium mediates high glucose-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells through CaMKII-CREB pathway

“…These results suggest that elevated [Ca 2+ ] i in retinal Müller cells can enhance HIF-1α expression, possibly triggering VEGF production. Many of the cellular responses to Ca 2+ are modulated by the CaMKs, among which CaMKII acts as a decoder of oscillating Ca 2+ signals [31] . Previous reports demonstrated that the autophosphorylation of CaMKII is highly expressed in neurons, regulating the cell cycle and transcription [32] , and the effects of CaMKII were mediated by CREB phosphorylation and CREB-dependent transcription.…”

Ca2+-stimulated Ca2+ Oscillations Produced by the Ca2+-sensing Receptor Require Negative Feedback by Protein Kinase C

“…It is recognized increasingly that the pattern and frequency of [Ca 2ϩ ] i oscillations play a key role in signal transduction, regulating Ca 2ϩ -and calmodulin-dependent protein kinase II (10), protein kinase C (11), mitochondrial metabolism (12), and nuclear transcriptional activity leading to differential gene expression (13)(14)(15)(16). Consequently, the elucidation of the mechanisms underlying the generation of [Ca 2ϩ ] i oscillations has attracted intense interest.…”

Visualizing dynamic interaction between calmodulin and calmodulin-related kinases via a monitoring method in live mammalian cells

“…According to the decoding hypothesis, the rate of association between CaMKIIα and calmodulin increases following an elevated frequency of Ca 2þ spikes. However, the dissociation rate remains constant and new associations can begin before dissociation ends completely (12,16). But the oscillatory interaction has not been shown under low frequency Ca 2þ spikes.…”

“…It has been proposed that calmodulin and CaMKIIα may exhibit an oscillatory interaction, since kinase activity is dependent upon the frequency of Ca 2þ spikes (12,16). According to the decoding hypothesis, the rate of association between CaMKIIα and calmodulin increases following an elevated frequency of Ca 2þ spikes.…”

“…To decode the signal and initiate the calcium signaling cascade, Ca 2þ -bound calmodulin undergoes a conformational change that induces interaction with various calmodulin-binding proteins, which in turn relay the signal (10). Calmodulin-dependent kinase IIα (CaMKIIα), one of the most studied calmodulin-binding proteins, is a multifunctional protein kinase that exists as a dodecameric complex; it decodes Ca 2þ spikes to regulate various cellular processes (11,12). Recently, CaMKIIα has been shown to function as a key regulator in synaptic plasticity, learning, and memory (13,14).…”