Insulin and the Stimulation of Glycogen Synthesis. The Road from Glycogen Structure to Glycogen Synthase to Cyclic Amp-Dependent Protein Kinase to Insulin Mediators

Author(s):  
Joseph Larner
2005 ◽  
Vol 25 (20) ◽  
pp. 9063-9072 ◽  
Author(s):  
Shin-ichiro Hino ◽  
Chie Tanji ◽  
Keiichi I. Nakayama ◽  
Akira Kikuchi

ABSTRACT The mechanism of cross talk between the Wnt signaling and cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]) pathways was studied. Prostaglandin E1 (PGE1), isoproterenol, and dibutyryl cAMP (Bt2cAMP), all of which activate PKA, increased the cytoplasmic and nuclear β-catenin protein level, and these actions were suppressed by a PKA inhibitor and RNA interference for PKA. PGE1 and Bt2cAMP also increased T-cell factor (Tcf)-dependent transcription through β-catenin. Bt2cAMP suppressed degradation of β-catenin at the protein level. Although PKA did not affect the formation of a complex between glycogen synthase kinase 3β (GSK-3β), β-catenin, and Axin, phosphorylation of β-catenin by PKA inhibited ubiquitination of β-catenin in intact cells and in vitro. Ser675 was found to be a site for phosphorylation by PKA, and substitution of this serine residue with alanine in β-catenin attenuated inhibition of the ubiquitination of β-catenin by PKA, PKA-induced stabilization of β-catenin, and PKA-dependent activation of Tcf. These results indicate that PKA inhibits the ubiquitination of β-catenin by phosphorylating β-catenin, thereby causing β-catenin to accumulate and the Wnt signaling pathway to be activated.


1988 ◽  
Vol 116 (1) ◽  
pp. 91-95 ◽  
Author(s):  
J. Rosenberg ◽  
M. Pines ◽  
S. Hurwitz

ABSTRACT Dispersed chick adrenocortical cells were incubated with avian parathyroid hormone (aPTH) or ACTH. Accumulation of cyclic AMP (cAMP), activity of cAMP-dependent protein kinase and the secretion of corticosterone and aldosterone, in response to these hormones, were measured. Accumulation of cAMP and activity of cAMP-dependent protein kinase were stimulated by both aPTH and ACTH as well as by cholera toxin. Cyclic AMP production followed a similar time-course when stimulated by either peptide hormone. Stimulation of steroid hormone secretion was detectable after 20 min of incubation with ACTH, but only after 40 min with aPTH. The maximal steroid hormone secretion by adrenocortical cells was similar when induced by either peptide hormone. The aPTH concentrations needed for half-maximal response of corticosterone and aldosterone secretion were higher than those for ACTH (2·5- and 2-fold respectively), but still within the physiological range. The 11β-hydroxylase inhibitor metyrapone inhibited the secretion of both corticosterone and aldosterone when induced by either aPTH or ACTH. The results suggest that aPTH is almost as potent as ACTH in stimulating the secretion of corticosterone and aldosterone from chick adrenocortical cells and utilizes a cAMP-dependent pathway similar to that of ACTH. J. Endocr. (1988) 116, 91–95


1989 ◽  
Vol 262 (2) ◽  
pp. 563-567 ◽  
Author(s):  
C Villar-Palasi ◽  
J J Guinovart ◽  
A M Gómez-Foix ◽  
J E Rodriguez-Gil ◽  
F Bosch

In rat hepatocytes, vanadate modifies neither the intracellular concentration of cyclic AMP nor the -cyclic AMP/+cyclic AMP activity ratio for cyclic AMP-dependent protein kinase. Vanadate can, however, counteract the increase in cyclic AMP and the increase in the -cyclic AMP/+cyclic AMP activity ratio of cyclic AMP-dependent protein kinase induced by glucagon. On the other hand, vanadate treatment of hepatocytes can produce a time- and concentration-dependent increase in cyclic AMP- and Ca2+-independent casein kinase activity. Maximal activation at the optimal time with 5 mM-vanadate was about 70% over control. A clear relationship was observed between the activation of casein kinase and the inactivation of glycogen synthase after vanadate treatment. These results suggest that casein kinase activity may be involved in vanadate actions in rat hepatocytes.


1976 ◽  
Vol 54 (3) ◽  
pp. 327-335 ◽  
Author(s):  
B. K. Tsang ◽  
R. L. Singhal

β-Adrenergic stimulation of the ventral prostate cyclic-AMP system was investigated by examining the influence of isoproterenol on endogenous cyclic-AMP levels as well as on the activities of adenylate cyclase (EC 4.6.1.1) and cyclic-AMP-dependent and independent protein kinases (EC 2.7.1.37). Administration of isoproterenol (1 mg/kg, ip) resulted in rapid elevation of adenylate cyclase activity (119%) and cyclic-AMP levels (593%). The observed isoproterenol-stimulated changes in cyclic-AMP metabolism of the ventral prostate were time-dependent and maximal stimulation was seen 5 min after treatment with this β-adrenergic agonist. The increases in prostatic adenylate cyclase and cyclic-AMP also were related to the dose of isoproterenol administered and maximal enhancement of these parameters was seen with 1 mg/kg dose of the agonist. Whereas pretreatment of rats with propranolol (3 mg/kg, ip) partially reversed these alterations, administration of an α-adrenergic antagonist, phentolamine, even at a dose of 5 mg/kg, failed to elicit any appreciable effect. Stimulation of prostatic soluble protein kinase by isoproterenol was associated with a decrease (33%) in the activity of the cyclic-AMP-dependent protein kinase with a concomitant increase (25%) in that of the independent enzyme. Whereas the ability of the enzyme to bind cyclic-[3H] AMP in vitro was decreased (54%) following isoproterenol treatment, the protein kinase activity ratio (−cyclic-AMP/+cyclic-AMP) was significantly elevated from 0.51 ± 0.05 to 0.95 ± 0.08. Although propranolol alone had little or no effect on these parameters, it inhibited partially the isoproterenol-induced alterations in cyclic-AMP-dependent protein kinase and the cyclic-AMP binding capacity. Treatment with propranolol also blocked the increases in the kinase activity ratio and in the activity of cyclic-AMP-independent enzyme seen with isoproterenol. Data suggest that the concentration of ventral prostate cyclic-AMP as well as the activities of adenylate cyclase and cyclic-AMP-dependent and independent form of protein kinases are subject to modulation by β-adrenergic stimulation.


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