Calmodulin-kinase II,

Other mechanisms have also been implicated in odor adaptation, including cAMP-dependent phosphorylation of ciliary proteins via protein kinase A G-protein-receptor kinase activity (GRK3), possibly via phosphorylation of the OR Ca2+/calmodulin kinase II (CaMKII) phosphorylation of ACIII cGMP and carbon monoxide [ 31 ]. These latter three mechanisms have been particularly linked to longer-lasting forms of adaptation, on the order of tens of seconds (for CaMKII) or minutes (CO/cGMP). Together with the short-term adaptation described above, these various molecular mechanisms provide the OSN with a number of ways to fine-tune odor responses over time. 

AC VIII, adenylyl cyclase type VIII BDNF, brain-derived neurotrophic factor CamKII, calcium-calmodulin kinase II GIRK2, G protein-activated inward rectifying potassium 2 MAOA, monoamine oxidase A n.d., not determined NCAM, neural cell adhesion molecule nNOS, neuronal nitric oxide synthase Petl, ETS domain transcription factor tPA, serine protease tissue-plasminogen activator (tPA). t/ > Increase/decrease in anxiety-related behavior. No effect. 

Cheetham SC, Crompton MR, Katona CL, Horton RW (1990) Brain 5-HTl binding sites in depressed suicides. Psychopharmacology (Berl) 102 544-548 Chen C, Rainnie DC, Greene RW, Tonegawa S (1994) Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II. Science 266 291-294... 

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]... 

Glutamate-mediated Ca2+ entry through NMDA at the plasma membrane level and mobilization of Ca2+from intracellular stores through PLC-mediated generation of PtdIns-3/J is indispensable for the basal NF-kB activity. Three cytosolic Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p2 l(ras)/phosphatidylinositol 3-kinase (Ptdlns-3K)/Akt pathways, are simultaneously involved in the steps linking the Ca2+ to NF-kB activity (Lilienbaum and Israel, 2003 Marchetti et al., 2004 Lubin et al., 2005). Calmodulin modulates calcineurin, a Ca2+-dependent protein phosphatase, which plays a role in the basal NF-kB activity, whilst stimulation of both the calmodulin kinase II and Akt kinase pathways results in the up-regulation of the transcriptional potential of the p65 subunit of NF-/cB (Lilienbaum and Israel,... 

Fog JU, Khoshbouei H, Holy M, Owens WA, Vaegter CB, Sen N, Nikandrova Y, Bowton E, McMahon DG, Colbran RJ, Daws LC, Sitte HH, Javitch JA, Galli A, Gether U (2006) Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport. Neuron 51 417—429. 

Meshul CK, Tan SE (1994) Haloperidol-induced morphological alterations are associated with changes in calcium/calmodulin kinase II activity and glutamate immunoreactivity. Synapse 75 205-217... 

Zhu WZ, Wang SQ, Chakir K, et al. Linkage of p,-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/ calmodulin kinase II. J Clin Invest 2003 111 617-625. 

Studies have revealed consequences of P-AR stimulation beyond regulating the rate and strength of myocyte contraction. Chronic stimulation of the PrAR induces myocyte apoptosis, although the signaling pathway is controversial (12,63,64). In vitro studies suggest that this process requires PKA-independent activation of intracellular Ca2+ through L-type Ca2+ channels, which leads to Ca2+ release from sarcoplasmic reticulum and subsequent activation of calmodulin kinase II in adult cardiac myocytes (65). However, this prAR-stimulated proapoptotic effect appears to be blocked by PKA inhibition in adult rat myocytes (63). In contrast, activation of P2-ARs has an antiapoptotic effect, which is mediated by the Py-subunits of G, in both rat and mouse adult cardiac myocytes... 

Gardoni F, Bellone C, Cattabeni F, Di Luca M. 2001. Protein kinase C activation modulates a-calmodulin kinase II binding to NR2A subunit of N-methyl-D-aspartate receptor. J. Biol. Chem. 276 7609-13... 

Leinders-Zufall T, Ma M, Zufall E 1999. Impaired odor adaptation in olfactory receptor neurons after inhibition of Ca" /calmodulin kinase II. J Neurosci 19 1-6. 

VI. POTENTIAL FUNCTIONS OF CALMODULIN-KINASE II IN SMOOTH MUSCLE... 

Several consensus sequence sites for phosphorylation by protein kinases A and C (PKC) and calmodulin kinase II are found in all of the cloned NOS isoforms however, the functional relevance of these sites has not been fully elucidated. It has, however, been demonstrated that the endothelial NOS undergoes phosphorylation following cell stimulation with receptor-dependent and -independent agonists (Robinson eta/., 1995), a phenomenon that could be completely inhibited by the calmodulin antagonist W-7 (Michel et al., 1993). PKC has also been reported to modulate NOS activity in cultured endothelial cells such that inhibition of PKC enhanced basal and agonist-stimulated NOS activity, whereas activation of PKC attenuated the release of NO (Hecker et al., 1993a Davada et al., 1994). It is unclear, however, whether the effects of such interventions reflect an effect of PKC on NOS itself, similar to the reported inhibition of brain NOS (Bredt et al.,... 

Silva AJ, Paylor R, Wehner JM, Tonegawa S. 1992a. Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. Science 257(5067) 206-211. 

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