Phosphorylation calmodulin kinase

Protein phosphorylation Calmodulin kinase I ATI Elongation factor-2 kinase Phosphorylase kinase Myosin Light Chain kinase... 

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. 

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]... 

During muscle contraction, l Caz+ is released from the sarcoplasmic reticulum. The Caz+ binds to the calmodulin subunit of phosphorylase kinase, activating it without phosphorylation. Phosphorylase kinase can then activate glycogen phosphorylase, causing glycogen degradation. 

Wu, G. Y., Deisseroth, K. and Tsien, R. W., 2001, Activity-dependent CREB phosphorylation convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway, Proc Natl Acad Sci USA, 98, pp 2808—13. 

An alternative mechanism by which cAMP may act to inhibit platelet function was proposed by Hathaway et al. (81). In this model (Figure 12), it is suggested that an increase in cAMP results in inhibition of myosin phosphorylation and consequent inhibition of platelet contractile activity (since unphos-phorylated myosin cannot interact with actin). Thus, it was proposed that cAMP causes the activation of a protein kinase which in turn phosphorylates myosin kinase. In the phosphory-lated form, myosin kinase is less capable of binding calmodulin and therefore is not as effective in phosphorylating myosin. 

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.,... 

Smooth muscle contractions are subject to the actions of hormones and related agents. As shown in Figure 17.32, binding of the hormone epinephrine to smooth muscle receptors activates an intracellular adenylyl cyclase reaction that produces cyclic AMP (cAMP). The cAMP serves to activate a protein kinase that phosphorylates the myosin light chain kinase. The phosphorylated MLCK has a lower affinity for the Ca -calmodulin complex and thus is physiologically inactive. Reversal of this inactivation occurs via myosin light chain kinase phosphatase. 

AMPK can also be activated by a Ca2+-mediated pathway involving phosphorylation at Thr-172 by the Ca2+/calmodulin-dependent protein kinase, CaMKK 3. CaMKKa and CaMKK 3 were discovered as the upstream kinase for the calmodulin-dependent protein kinases-1 and -IV they both activate AMPK in a Ca2+/ calmodulin-dependent manner in cell-free assays, although CaMKK 3 appears to much more active against AMPK in intact cells. Expression of CaMKKa and CaMKK(3 primarily occurs in neural tissues, but CaMKKp is also expressed in some other cell types. Thus, the Ca2+-mediated pathway for AMPK activation has now been shown to occur in response to depolarization in rat neuronal tissue, in response to thrombin (acting via a Gq-coupled receptor) in endothelial cells, and in response to activation of the T cell receptor in T cells. 

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

This kinase specifically phosphorylates the regulatory light chain of myosin after activation by calcium-calmodulin. Several isozymes of approximately 135 kDa exist. 

The major relaxing transmitters are those that elevate the cAMP or cGMP concentration (Fig. 3). Adenosine stimulates the activity of cAMP kinase. The next step is not clear, but evidence has been accumulated that cAMP kinase decreases the calcium sensitivity of the contractile machinery. In vitro, cAMP kinase phosphorylated MLCK and decreased thereby the affinity of MLCK for calcium-calmodulin. However, this regulation does not occur in intact smooth muscle. Possible other substrate candidates for cAMP kinase are the heat stable protein HSP 20, (A heat stable protein of 20 kDa that is phosphorylated by cGMP kinase. It has been postulated that phospho-HSP 20 interferes with the interaction between actin and myosin allowing thereby smooth muscle relaxation without dephosphorylation of the rMLC.) Rho A and MLCP that are phosphorylated also by cGMP kinase I (Fig. 3). 

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