PKA-catalyzed phosphorylation

Perpetuation of the PKA-mediated phosphorylation signal is regulated by specific and nonspecific phosphatases that catalyze the removal of phosphate from the PKA substrates. The termination of the cAMP signal is mediated by its degradation to 5 -AMP by cyclic... 

Other studies have demonstrated that the skeletal muscle ai peptide can be phosphorylated in T-tubule membranes by a multifunctional Ca " /calmodulin (CaM)-dependent protein kinase [111], Phosphorylation occurs on the i subunit to an extent of 2 mol phosphate/mol subunit and on the /i subunit to an extent of 0.7-1 mol phosphate/mol channel [108,111]. Phosphorylation catalyzed by the CaM-kinase on the ai subunit is additive to that caused by PKA and occurs on distinct sites [111]. So far, however, we have not observed any functional consequences of phosphorylation of the skeletal muscle Ca channels by the CaM-kinase. 

The principal component of heterologous (agonist-independent) desensitization of GPCRs is the rapid phosphorylation catalyzed by PKC and cAMP-dependent protein kinase (PKA). In studies using primary cultures and recombinant systems, the role of kinase-mediated phosphorylation of intracellular serines or threonines for the desensitization of the mGluR has been investigated (92-101). 

Phosphorylation of HI during mitosis is catalyzed by the cyclin B-Cdc2 kinase, a tightly regulated enzyme [25,26]. In Tetrahymena mitotically dividing nuclei, cyclic-AMP dependent kinase (PKA) or PKA-like kinase phosphorylates HI [27,28]. Protein phosphatase 1 dephosphorylates the phosphorylated HI [29]. 

The self-phosphorylation process catalyzed by many protein kinases as part of the regulatory mechanism for their own activation. Because true autophosphorylation is a unimolecular reaction involving enzyme both as catalyst and phosphoryl acceptor, the fraction of autophosphory-lated enzyme at any time after addition of ATP (or another phosphoryl donor) will be independent of the initial concentration of the enzyme. This criterion was first applied to the autophosphorylation of cardiac muscle cyclic AMP-stimulated protein kinase, now designated protein kinase A (PKA). At a fixed concentration of MgATP , the fraction of autophosphorylated protein will follow the first-order rate laws, [A]/[A ] where k is a first-order rate constant. 

One downstream effect of epinephrine is to activate glycogen phosphorylase b. This conversion is promoted by the enzyme phosphorylase b kinase, which catalyzes the phosphorylation of two specific Ser residues in phosphorylase b, converting it to phosphorylase a (see Fig. 6-31). Cyclic AMP does not affect phosphorylase b kinase directly. Rather, cAMP-dependent protein kinase, also called protein kinase A or PKA, which is allosterically activated by cAMP (Fig. 12-12, step (5)), catalyzes the phosphorylation of inactive phosphorylase b kinase to yield the active form. 

First, the binding of one hormone molecule to one receptor catalytically activates several Gs molecules. Next, by activating a molecule of adenylyl cyclase, each active Gsa molecule stimulates the catalytic synthesis of many molecules of cAMP. The second messenger cAMP now activates PKA, each molecule of which catalyzes the phosphorylation of many molecules of the target protein—phosphorylase b kinase in Figure 12-16. This... 

Intramolecular five-membered ring formation occurs in the alkaline-catalyzed hydrolysis of a series of esters of 2-hydroxypropylphosphate, where a linear free-energy relationship is found for the rate of alkoxide expulsion as a function of the pKa of the alcohol. No evidence for phosphoryl migration was obtained consistent with the fact that pseudorotation of the presumed intermediate leading to ring opening would be inhibited (50), viz. 

Figure 8 Simplified diagram of a signaling cascade that involves NE, BDNF, and CREB after NE acts on the postsynaptic fi-noradrenergic receptor. NE couples to a G protein (Gas), which stimulates the production of cAMP from adenosine triphosphate (ATP). This reaction is catalyzed by adenylate cyclase (AC). cAMP activates protein kinase A (PKA). Inside the cell, PKA phosphorylates (P) the CREB protein, which binds upstream from specific regions of genes and regulates their expression. BDNF is one target of cAMP signaling pathways in the brain. CRE, cyclic AMP regulatory element ER, endoplasmic reticulum, [reprinted from Reference 76 with permission of the author and the publisher, Canadian Medical Association].

Reversible covalent modification. The catalytic properties of many enzymes are markedly altered by the covalent attachment of a modifying group, most commonly a phosphoryl group. ATP serves as the phosphoryl donor in these reactions, which are catalyzed by protein kinases. The removal of phosphoryl groups by hydrolysis is catalyzed by protein phosphatases. This chapter considers the structure, specificity, and control of protein kinase A (PKA), a ubiquitous eukaryotic enzyme that regulates diverse target proteins. 

When ANP binds to its target cell in the renal tubule, it provokes the activation of a protein kinase. The kinase, in turn, catalyzes the phosphorylation and inactivation of Na,K-ATPase. Na,K-ATPase is a vital membrane-bound protein in most, or all, cells of the body, as mentioned earlier. Its inhibition in the renal tubule results in decline in sodium resorption (Wang and Robinson, 1997). The exact kinase that is involved is not certain, but it appears to be protein kinase A (PKA) (Ledoux et al, 1997 Belusa et al, 1997). 

---