Direct evidence that the protein kinase catalytic subunit mediates the effects of cAMP on tyrosine aminotransferase synthesis.

Boney, Charlotte M.; Fink, Donald W.; Schlichter, D; Carr, Kay; Wicks, Wesley D.

doi:10.1016/s0021-9258(18)32514-6

Cited by 47 publications

(5 citation statements)

References 30 publications

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“…Maximal activation by forskolin-induced cAMP accumulation led to a rapid translocation of C to the nucleus, which was reversible upon removal of forskolin (Nigg et al, 1985b). Together with other reports on the activation of certain genes by cAMP-dependent protein kinases (Maurer, 1981;Murdoch et al, 1982;Lamers et al, 1982;Boney et al, 1983;Jungmann et al, 1983;Lewis et al, 1983), these data may suggest that protein kinase II is dissociated only after a strong stimulus as evoked by high levels of cAMP, thus allowing induction of key enzymes by specific gene activation. Special functions of protein kinase II are also indicated by the existence of tissue-specific isoforms of R II subunits (Erlichman et al, 1980;Robinson-Steiner et al, 1984;Jahnsen et al, 1985).…”

Section: Discussionsupporting

confidence: 64%

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cAMP-dependent protein kinases I and II: divergent turnover of subunits

Weber¹,

Hilz²

1986

Biochemistry

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cAMP-dependent protein kinase subunits were isolated from livers of rats that had been subjected to biosynthetic labeling with radioactive leucine. By application of ligand and antibody affinity techniques pure regulatory (R I; R II) and catalytic (C) subunits could be obtained in high yields, which allowed measurement of the apparent degradation rate constants and half-lives following a double isotope labeling protocol. In this way marked differences of apparent half-lives of regulatory subunits R I (t1/2 = 31 h) and R II (t1/2 = 125 h) were observed. To avoid the negative influence of reutilization inherent in the decay experiments, specific radioactivities were determined after a short isotope pulse. This parameter, which under steady-state conditions reflects the fractional turnover rate of the subunits, was found to be different for all three protein kinase subunits. Relative to total liver protein, the ratios R I:R II:C corresponded to 3.9:0.6:2. Our data indicate that in each type of protein kinase isoenzymes regulatory and catalytic subunits turn over with similar rates. The type I isoenzyme, however, is renewed much faster than protein kinase II. Furthermore, our findings are consistent with the thesis that free subunits as generated by activation are more susceptible to degradation than the holoenzymes, leading under steady-state conditions to compensatory resynthesis. Since renewal of R I exceeded that of R II also in two other tissues, the elevated turnover of protein kinase I as an indicator of preferential activation appears to be a general phenomenon. The different turnover of the two isoenzymes, then, may relate to different cellular functions like modulation of enzyme activity vs. modulation of gene activity.

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Section: Discussionsupporting

confidence: 64%

“…0006-2960/86/0425-566 ISO 1.50/0 ciated holoenzyme II under conditions of maximal stimulation (Nigg et al, 1985b) as well as other data on a nuclear function of C (Maurer, 1981;Murdoch et al, 1982;Lamers et al, 1982;Boney et al, 1983;Jungmann et al, 1983; Lewis et al, 1983) lend support to such an interpretation.…”

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confidence: 82%

cAMP-dependent protein kinases I and II: divergent turnover of subunits

Weber¹,

Hilz²

1986

Biochemistry

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“…Results presented here show that neither intracellular cAMP levels nor cAMPinducible gene transcription was affected by fibroblast TSEJ. Furthermore, TSEI affected both basal and glucocorticoidinducible TAT expression, and neither of these activities is cyclic nucleotide dependent (1). Finally, cAMP-responsive elements lie within 120 base pairs of the PEPCK cap site (26,35), whereas sequences required for TSE1 regulation map further upstream (unpublished observations).…”

Section: Resultsmentioning

confidence: 94%

“…Recent studies have identified two distinct genetic loci that are involved in extinction of liver gene activity in hepatoma hybrid cells (13,15,23,24). The first such locus, tissuespecific extinguisher 1 (TSEI), is a discrete genetic entity that resides on mouse chromosome 11 and human chromosome 17. TSEI extinguishes tyrosine aminotransferase (TAT) (13), phosphoenolpyruvate carboxykinase (PEPCK) (15), and argininosuccinate synthetase (AS) (this report) expression in trans, but it has no effect on expression of most other liver genes.…”

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confidence: 99%

Hormonal Regulation of TSE1 -Repressed Genes: Evidence for Multiple Genetic Controls in Extinction

Thayer

Fournier

1989

Molecular and Cellular Biology

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Somatic cell hybrids formed by fusing hepatoma cells with fibroblasts generally fail to express liver functions, a phenomenon termed extinction. Previous studies demonstrated that extinction of the genes encoding tyrosine aminotransferase, phosphoenolpyruvate carboxykinase, and argininosuccinate synthetase is mediated by a specific genetic locus (TSE1) that maps to mouse chromosome 11 and human chromosome 17. In this report, we show that full repression of these genes requires a genetic factor in addition to TSE1. This conclusion is based on the observation that residual gene activity was apparent in monochromosomal hybrids retaining human TSE1 but not in complex hybrids retaining many fibroblast chromosomes. Furthermore, TSE1-repressed genes were hormone inducible, whereas fully extinguished genes were not. Analysis of hybrid segregants indicated that genetic loci required for the complete repression phenotype were distinct from TSE1.

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“…The major limitation of the liposome procedure lies in the fact that adherent liposomes containing the substance to be injected, remain attached to the cells so that it is difficult to determine how much of the substance in question has actually been delivered to the interior of the cell. The use of erythrocyte ghosts provides a possible solution to this problem since injection is efficient (e.g., references 3,14), and the erythro-cytes can be destroyed by lysis after injecting their contents, with the result that uninjected material is removed (14). It was decided to determine whether DNase I, injected via erythrocyte ghosts into Y-1 cells, is capable of inhibiting the steroidogenic responses of these cells to ACTH and dibutyryl cyclic AMP, Since pancreatic DNase I is known to bind to G-actin in a quantitative manner (34) and thereby to prevent polymerization ofactin, this approach has enabled us to study the role of actin in the responses to the two stimulating agents in greater detail.…”

mentioning

confidence: 99%

Role of actin in the responses of adrenal cells to ACTH and cyclic AMP: inhibition by DNase I.

Osawa

Betz²,

Hall³

1984

The Journal of Cell Biology

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Erythrocyte ghosts were loaded with pancreatic DNase I and fused with Y-1 adrenal tumor cells to test the possibility that this enzyme might inhibit the steroidogenic responses of the cells to ACTH and cyclic AMP. Fusion of erythrocyte ghosts loaded with DNase I, but not those containing albumin, ovalbumin, boiled DNase I, or DNase I with excess G-actin, inhibited the increase in production of 20a-dihydroprogesterone produced by ACTH and dibutyryl cyclic AMP; inhibition was concentration-dependent with 50% inhibition by 3 x 107 molecules of DNase I per cell. It was found that inhibition by DNase I was exerted at the step in the steroidogenic pathway at which cholesterol is transported to mitochondria where steroidogenesis begins. This was shown by measuring transport of cholesterol into the inner mitochondrial membrane, by measuring the production of pregnenolone by isolated mitochondria and by demonstrating that DNase I was without effect on the conversion of pregnenolone to 20a-dihydroprogesterone (an end-product of steroid synthesis). The actin content of Y-1 cells was measured by two methods based upon inhibition of DNase I and by SDS gels following centrifugation. The cells were found to contain 2-3 x 107 molecules of actin per cell of which two-thirds is present as G-actin. Since DNase I is known to bind to G-actin to give a one to one complex, these and other findings suggest that at least some of the G-actin in the cells may be necessary for the steroidogenic responses to ACTH and cyclic AMP.

show abstract

Direct evidence that the protein kinase catalytic subunit mediates the effects of cAMP on tyrosine aminotransferase synthesis.

Cited by 47 publications

References 30 publications

cAMP-dependent protein kinases I and II: divergent turnover of subunits

cAMP-dependent protein kinases I and II: divergent turnover of subunits

Hormonal Regulation of TSE1 -Repressed Genes: Evidence for Multiple Genetic Controls in Extinction

Role of actin in the responses of adrenal cells to ACTH and cyclic AMP: inhibition by DNase I.

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