Protein kinase calcium requirement

Furthermore, PKCe is required for nerve growth factor-induced activation of mitogen-activated protein kinases and neurite outgrowth by ethanol. It is also required for ethanol-induced increases in N-type voltage-gated calcium channels in PC 12 neural cells. 

Lead also has been shown to substitute for calcium in the activation of calmodulin, but this requires higher levels of lead than does the activation of protein kinase C. Nevertheless, the affinity of lead for calmodulin is higher than that of calcium. Once activated, calmodulin regulates the activity of certain enzymes and transporters. For example, it activates c-AMP phosphodiesterase to hydrolyze and terminate the action of cAMP, another second messenger (Bressler and Goldstein 1991 Goldstein 1993 Goering 1993). 

FIGURE 1 2-2 Schematic diagram of the phosphorylation sites on each of the four 60kDa subunits of tyrosine hydroxylase (TOHase). Serine residues at the N-terminus of each of the four subunits of TOHase can be phosphorylated by at least five protein kinases. (J), Calcium/calmodulin-dependent protein kinase II (CaM KII) phosphorylates serine residue 19 and to a lesser extent serine 40. (2), cAMP-dependent protein kinase (PKA) phosphorylates serine residue 40. (3), Calcium/phosphatidylserine-activated protein kinase (PKC) phosphorylates serine 40. (4), Extracellular receptor-activated protein kinase (ERK) phosphorylates serine 31. (5), A cdc-like protein kinase phosphorylates serine 8. Phosphorylation on either serine 19 or 40 increases the activity of TOHase. Serine 19 phosphorylation requires the presence of an activator protein , also known as 14-3-3 protein, for the expression of increased activity. Phosphorylation of serines 8 and 31 has little effect on catalytic activity. The model shown includes the activation of ERK by an ERK kinase. The ERK kinase is activated by phosphorylation by PKC. (With permission from reference [72].)... 

The synthesis of 5-HT can increase markedly under conditions requiring more neurotransmitter. Plasticity is an important concept in neurobiology. In general, this refers to the ability of neuronal systems to conform to either short- or long-term demands placed upon their activity or function (see Plasticity in Ch. 53). One of the processes contributing to neuronal plasticity is the ability to increase the rate of neurotransmitter synthesis and release in response to increased neuronal activity. Serotonergic neurons have this capability the synthesis of 5-HT from tryptophan is increased in a frequency-dependent manner in response to electrical stimulation of serotonergic soma [7]. The increase in synthesis results from the enhanced conversion of tryptophan to 5-HTP and is dependent on extracellular calcium ion. It is likely that the increased 5-HT synthesis results in part from alterations in the kinetic properties of tryptophan hydroxylase, perhaps due to calcium-dependent phosphorylation of the enzyme by calmodulin-dependent protein kinase II or cAMP-dependent protein kinase (PKA see Ch. 23). 

This enzyme [EC 2.7.1.123], also referred to as calcium/ calmodulin-dependent protein kinase type II, and micro-tubule-associated protein MAP2 kinase, catalyzes the reaction of ATP with a protein to produce ADP and an 0-phosphoprotein. The enzyme requires calcium ions and calmodulin. Proteins that can serve as substrates include vimentin, synapsin, glycogen synthase, the myosin light-chains, and the microtubule-associated tau protein. This enzyme is distinct from myosin light-chain kinase [EC 2.7.1.117], caldesmon kinase [EC 2.7.1.120], and tau-protein kinase [EC 2.7.1.135]. 

Chow, F. A., Anderson, K. A., Noeldner, P. K. and Means, A. R., 2005, The autonomous activity of calcium/calmodulin-dependent protein kinase IV is required for its role in transcription, J Biol Chem, 280, pp 20530-8. 

Sutton KG, McRory JE, Guthrie H, Murphy TH, Snutch TP (1999) P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-lA. Nature 401 800-4 Swartz KJ (1993) Modulation of Ca2+ channels by protein kinase C in rat central and peripheral neurons disruption of G protein-mediated inhibition. Neuron 11 305-20 Swartz KJ, Merritt A, Bean BP, Lovinger DM (1993) Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission. Nature 361 165-8 Takahashi SX, Miriyala J, Colecraft HM (2004) Membrane-associated guanylate kinase-like properties of beta-subunits required for modulation of voltage-dependent Ca2+ channels. Proc Natl Acad Sd US A 101 7193-8... 

Hung CH, Henshaw DR, Wang CC-B, Mauck RL, Raia F, Palmer G, Chao P-HG, Mow VC, Ratcliffe A, Valhmu WB. Mitogen-activated protein kinase signaling in bovine articular chondrocytes in response to fluid flow does not require calcium mobilization. J Biomech. 2001 33 73-80. 

A calcium regulated enzyme or protein could be considered as the third type of calcium binding protein. The calcium regulated enzyme is contrasted to the target protein of the calcium dependent regulatory protein in that the calcium regulated enzymes are capable of binding calcium directly and do not require additional proteins to confer calcium sensitivity. An example of this type of calcium receptor is the protein kinase C [8]. 

The exact function of the annexin fold family is at present unclear. All of these proteins appear to show calcium-dependent binding to phosphatidylethanolamine or phosphatidylinositol liposomes. In addition, they can promote fusion of liposomes, and because of this property, it has been suggested that these proteins might mediate calcium dependent exocytosis. P36 and p35 have also been shown to bind to F-actin and spectrin [65,66]. Recently, Khanna et al. [70] have reported a procedure for the simultaneous purification of p35, p36 oligomer and p36 monomer from bovine lung, and identified all three proteins as substrates of protein kinase C. Furthermore, the work of Huang et al. [86] and Khanna et al. [69] has suggested that all three proteins are inhibitors of phospholipase A2. Further experiments will be required to clarify the function of these proteins. 

Phosphorylase kinase is one of the best characterized enzyme systems to illustrate the role of calcium ions in regulation of intermediary metabolism. Phosphorylase kinase is composed of four different subunits termed a (Mr 145000), /3 (MT 128000), y (A/r 45000) and 5 (Mr 17000) and has the structure (a/3y8)A [106]. Only one of its four subunits actually catalyses the phosphorylation reaction the other three subunits are regulatory and enable the enzyme complex to be activated both by calcium and cyclic AMP. The y subunit carries the catalytic activity the 8 subunit is the calcium binding protein calmodulin and is responsible for the calcium dependence of the enzyme. The a and /3 subunits are the targets for cyclic-AMP mediated regulation, both being phosphorylated by the cyclic-AMP dependent protein kinase. Calmodulin appears to interact with phosphorylase kinase in a different manner from other enzymes, since it is an integral component of the enzyme. Phosphorylase kinase has an absolute requirement for calcium, and is inactive in its absence. 

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