Ca2+-Calmodulin complex

The Ca2+-calmodulin complex may also activate nitric oxide synthase (NOS), which binds to a PDZ domain of PSD-95. Activated NOS produces NO from arginine NO, in turn, activates guanylate cyclase, the enzyme that catalyzes the conversion of GTP to the intracellular messenger cGMP, which activates protein kinase G (PKG). 

CaM kinase II <1, 3> ( phosphorylates and activates [26] <3> phosphorylation of Thr-311 results in 8-lOfold enzyme activation in the presence of 0.01 mM free Ca " and 0.002 mM calmodulin and in a 25fold increase in sensitivity to the Ca /calmodulin complex [26] <1,3> phosphorylation of isoenzyme B by calmodulin kinase II and protein kinase C added together results in a maximal 60-70fold activation, no effect on the sensitivity to the Ca2 /calmodulin complex, CaM kinase II alone activates 35-40fold in the presence of Ca " and calmodulin [28] <1> endogenous activator of isoform A [30]) [26, 28, 30]... 

In addition to JAKs, STAT1 is also directly phosphorylated by protein kinase C. This process is mediated by inositol triphosphate, Ca2+ release, formation of Ca2+-calmodulin complex and release of calcineurin. Calcineurin dephosphorylates NF-AT resulting in its translocation to the nucleus and subsequent activation of STAT1, in addition to other genes. 

A primary target of intracellular Ca2+ is calmodulin and the Ca2+/calmodulin complex in turn promotes the concomitant activation of the calmodulin-dependent... 

The PM Ca2+-ATPase is activated by the Ca2+—calmodulin complex (calmodulin being a key Ca2+-binding regulatory protein) and the ER Ca2+-ATPase is stimulated by the... 

CA, carbonic anhydrase Ca2+ CH, Ca2+ channel Ca2+, -CaM, Ca2+, -calmodulin complex Ca2+-K+ CH, Ca2+-dependent K+ channel CAB Pase, cyclic AMP-binding phosphatase CABNase, cyclic nucleotide-binding nucleotidase... 

With the help of NMR measurement, it has been shown that the Ca2+/calmodulin complex has a flexible structure. Flexibility is probably of great importance for the function of Ca2+/calmodulin. Structural information on Ca2+/calmodulin bound to substrates is only available for peptides derived from target proteins. In the complex with peptide substrates (Fig. 6.13), Ca2+/calmodulin has a collapsed structure in which the two globular domains are much closer together than in free Ca2+/calmodulin, and it wraps around and sequesters the helical calmodulin-binding peptides. 

The Ca2+/calmodulin complex is a signal molecule that is involved in many signal transduction pathways. Ca2+/calmodulin is involved, e. g., in regulation of proliferation, mitosis, neuronal signal transduction, muscle contraction and glucose metabo-... 

The special feature of regulation of CaM kinase II is the memory effect within the activation process. Activation of the enzyme is initiated by a generally transient increase in cellular Ca2+. Ca2+ activates CaM kinase II in the form of the Ca2+/calmodulin complex the kinase remains active even after the Ca2+ signal has died away, because the enzyme is converted into an autonomous activated state upon autophosphorylation. Presumably the complex holoenzyme structure of CaM kinase II endows the kinase with this unique regulatory property, allowing it to function as a sensor of cellular Ca2+ oscillations. 

The production of NO in vascular endothelium as well as in other cell types is catalyzed by the enzyme nitric oxide synthase (NOS). Three different classes of NOS have been described through cloning techniques and other approaches (1) an endothelial form of NOS whose activity is stimulated by the binding of the Ca2+-calmodulin complex upon cellular activation of Ca2+ mobilization (2) a neural form of NOS whose activation is through a similar mechanism (i.e., intracellular Ca2+ mobilization) but whose properties are distinct from the endothelial enzyme and (3) an in-... 

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