Calcium/calmodulin-dependent protein kinase II (CaMKII) localization acts in concert with substrate targeting to create spatial restriction for phosphorylation.

@article{Tsui2005, abstract = {Ca2+/calmodulin-dependent protein kinase II (CaMKII) acts in diverse cell types by phosphorylating proteins with key calcium-dependent functions such as synaptic plasticity, electrical excitability, and neurotransmitter synthesis. CaMKII displays calcium-dependent binding to proteins in vitro and translocation to synaptic sites after glutamatergic activity in neurons. We therefore hypothesized that subcellular targeting of CaMKII can direct its substrate specificity in an activity-dependent fashion. Here, we examined whether activity-dependent colocalization of CaMKII and its substrates could result in regulation of substrate phosphorylation in cells. We find that substrates localized at cellular membranes required CaMKII translocation to these compartments to achieve effective phosphorylation. Spatial barriers to phosphorylation could be overcome by translocation and anchoring to the substrate itself or to nearby target proteins within the membrane compartment. In contrast, phosphorylation of a cytoplasmic counterpart of the substrate does not require CaMKII translocation or stable protein-protein binding. Cytosolic phosphorylation is more permissive, exhibiting partial calcium-independence. Localization-dependent substrate specificity can also show more graded levels of regulation within signaling microdomains. We find that colocalization of translocated CaMKII and its substrate to lipid rafts in the plasma membrane can modulate the magnitude of phosphorylation. Thus, dynamic regulation of both substrate and kinase localization provides a powerful and nuanced way to regulate CaMKII signal specificity.}, author = {Tsui, Jennifer and Inagaki, Masaki and Schulman, Howard }, citeulike-article-id = {2054459}, doi = {10.1074/jbc.M407653200}, journal = {J Biol Chem}, keywords = {article-predikin, calcium-calmodulin-dependent, cell, chain, fusion, human, kinase, kinetics, line, membrane, microdomains, phosphorylation, polymerase, protein, reaction, recombinant, signal, transduction, transfection, transport, type}, month = {Mar}, number = {10}, pages = {9210--9216}, posted-at = {2007-12-04 03:22:14}, priority = {2}, title = {Calcium/calmodulin-dependent protein kinase II (CaMKII) localization acts in concert with substrate targeting to create spatial restriction for phosphorylation.}, url = {http://dx.doi.org/10.1074/jbc.M407653200}, volume = {280}, year = {2005} }

TY - JOUR ID - Tsui2005 L3 - citeulike-article-id:2054459 TI - Calcium/calmodulin-dependent protein kinase II (CaMKII) localization acts in concert with substrate targeting to create spatial restriction for phosphorylation. JF - J Biol Chem VL - 280 IS - 10 SP - 9210 EP - 9216 N2 - Ca2+/calmodulin-dependent protein kinase II (CaMKII) acts in diverse cell types by phosphorylating proteins with key calcium-dependent functions such as synaptic plasticity, electrical excitability, and neurotransmitter synthesis. CaMKII displays calcium-dependent binding to proteins in vitro and translocation to synaptic sites after glutamatergic activity in neurons. We therefore hypothesized that subcellular targeting of CaMKII can direct its substrate specificity in an activity-dependent fashion. Here, we examined whether activity-dependent colocalization of CaMKII and its substrates could result in regulation of substrate phosphorylation in cells. We find that substrates localized at cellular membranes required CaMKII translocation to these compartments to achieve effective phosphorylation. Spatial barriers to phosphorylation could be overcome by translocation and anchoring to the substrate itself or to nearby target proteins within the membrane compartment. In contrast, phosphorylation of a cytoplasmic counterpart of the substrate does not require CaMKII translocation or stable protein-protein binding. Cytosolic phosphorylation is more permissive, exhibiting partial calcium-independence. Localization-dependent substrate specificity can also show more graded levels of regulation within signaling microdomains. We find that colocalization of translocated CaMKII and its substrate to lipid rafts in the plasma membrane can modulate the magnitude of phosphorylation. Thus, dynamic regulation of both substrate and kinase localization provides a powerful and nuanced way to regulate CaMKII signal specificity. KW - article-predikin KW - calcium-calmodulin-dependent KW - cell KW - chain KW - fusion KW - human KW - kinase KW - kinetics KW - line KW - membrane KW - microdomains KW - phosphorylation KW - polymerase KW - protein KW - reaction KW - recombinant KW - signal KW - transduction KW - transfection KW - transport KW - type AU - Tsui, Jennifer AU - Inagaki, Masaki AU - Schulman, Howard PY - 2005/Mar// UR - http://dx.doi.org/10.1074/jbc.M407653200 ER -