What regulates secretion of non-stored proteins by eukaryotic cells?

Protein secretion is conventionally viewed as taking place by either of two cellular routes, a regulated pathway, involving external stimuli and secretory granules, and a presumptive ‘constitutive’ pathway, which does not involve hormonal or neuronal stimuli or the production of secretory granules. The evidence reviewed here strongly suggests that there are post-synthesis rate-limiting steps for many proteins released by the ‘constitutive’ pathway and, hence, that regulation in some sense is involved here too. The nature of these rate-limiting determinants and events is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50183/1/950040507_ftp.pd

Comparison on effects of phenobarbital and nicotine on nuclear protein synthesis in rat liver

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33666/1/0000176.pd

Alteration of enzyme activity in rat liver following the acute and chronic administration of nicotine

The ip injection of nicotine (2 or 4 mg/kg) to rats produced an increase in tryptophan pyrrolase activity in liver within 2 hours after drug administration. The elevation in enzyme activity reached a peak at 4 hours after drug injection and returned toward control levels by 6 hours. Administration of 4 mg of nicotine per kilogram to rats 4 times a day for 3 consecutive days produced an elevation of ethylmorphine and norcodeine metabolism in postmitochondrial supernatant fractions from liver. The chronic administration of nicotine (5.9 mg/kg/day) in the drinking water for 7 days produced an elevation in the metabolism of ethylmorphine, norcodeine, and aniline by liver microsomes. This increased enzyme activity was maintained for 5 weeks when nicotine was continued at that dose. However, if the dose was lowered below 4.4 mg/kg/day, the increased activity was not maintained. The activities of tryptophan pyrrolase and tyrosine transaminase were not altered by chronic drug treatment. An increase in the capacity of liver microsomes to synthesize protein was observed when nicotine treatment was continued for 4 weeks. These data indicate (1) that an elevation of microsomal drug-metabolizing enzymes can be achieved after the acute administration of nicotine, but only when convulsive doses are given several times a day, suggesting that the increased activity after acute drug treatment may be a stress-related event; and (2) that the chronic administration of nicotine can increase the activity of drug-metabolizing enzymes, possibly by inducing enzyme synthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32765/1/0000136.pd

Presence of multiple protein kinase activities in rat liver nuclei

Protein kinase activity was found in the acidic nuclear protein fraction extracted from rat liver nuclei. Four distinct kinase activities were separated by phosphocellulose and DEAE-Sephadex chromatography. Additional evidence for separate enzyme activities is based on differences in pH optimum, enzyme stability, and substrate specificity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34156/1/0000442.pd

Synthesis and phosphorylation of chromatin-associated proteins in cAMP-induced "differentiated" neuroblastoma cells in culture

Prostaglandin E1 and a cAMP phosphodiesterase inhibitor 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, RO20-1724, were used to induce differentiation in mouse neuroblastoma cells in culture. The incorporation of amino acids and phosphate into nuclear proteins of control and drug-treated cells (1 h and 3 days after treatment) was examined using double radioisotopic techniques. A marked decrease in histone synthesis and H1-histone phosphorylation were observed in `differentiated' neuroblastoma cells after 3 days of prostaglandin E1 and RO20-1724 treatment, but only small differences were noted in the synthesis and phosphorylation of non-histone chromatin associated proteins after 3 days of drug treatment. Minimal changes were observed in the labeling of histone and non-histone nuclear proteins if the cells were treated for 1 h with prostaglandin E1 and RO20-1724.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21755/1/0000149.pd

Effects of the carcinogen methylazoxymethanol acetate on protein synthesis and drug metabolism in rat livers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33576/1/0000079.pd

An oligosaccharide of the O-linked type distinguishes the free from the combined form of hCG [alpha] subunit

JAR malignant trophoblast cells produce a free [alpha] subunit in addition to an [alpha] combined with [beta] subunit as hCG. The free [alpha] is larger by gel chromatography and SDS-PAGE than combined [alpha] and is unable to associate with [beta] subunit to form hCG. A tryptic fragment, representing amino acid residues 36-42, derived from free [alpha] was larger than the corresponding fragment from combined [alpha]. After neuraminidase treatment, the fragment from free [alpha] bound peanut lectin agarose, which is specific for Gal[beta]1-3GalNAc as found in O-linked oligosaccharides. The fragment also contained Gal and GalNAc (and a lesser amount of GlcNAc) as determined by glycosidase sensitivity and amino sugar analyses. Removal of this tryptic fragment ablated the size difference between free and combined [alpha] subunits.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24721/1/0000143.pd

The cytokinetic and cytotoxic effects of ICRF-159 and ICRF-187 in vitro and ICRF-187 in human bone marrow in vivo

The cytotoxic and cytokinetic effects of ICRF-159 and its d-enantiomer ICRF-187 have been examined in vitro . The effects of both agents were identical. Cytotoxicity is dependent on both the drug concentration and the duration of drug exposure. Drug exposure for twice the cell cycle time is necessary for maximum effect. Cytotoxicity is also dependent upon the rate of cell proliferation. A rapidly growing cell population is more sensitive to brief drug exposure than a slowly growing population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45135/1/10637_2004_Article_BF00177411.pd

Equilibrium dialysis studies on two lima bean lectins

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22241/1/0000677.pd

Role of 3',5'-cyclic AMP in the control of nuclear protein kinase activity

The role of cAMP in the regulation of nuclear protein kinase activity was investigated. Acidic nuclear proteins prepared from rat liver nuclei were separated by phosphocellulose chromatography into four peaks of protein kinase activity and two peaks of cAMP-binding activity. A fraction which bound cAMP also inhibited the most active nuclear protein kinase, K IV, and the inhibition was diminished in the presence of 5 [mu]M cAMP. Further support for the regulation of nuclear kinases by cAMP was obtained using a regulatory subunit prepared from rabbit muscle protein kinase. The muscle regulatory subunit markedly inhibited liver nuclear kinase activities. The addition of cAMP partially restored the activities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33814/1/0000070.pd