Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammary glands from parous mice required lower concentrations of hormones in vitro than those from virgins to effect differentiation, as measured by lactose synthetase activity. This phenomenon could not be explained by changes in receptor levels, since both mammary gland insulin and prolactin binding, although elevated at midpregnancy, returned to baseline in tissue from parous mice. Ethidium bromide, an intercalating dye, was a potent inhibitor of lactose synthetase induction in explants from virgins but much less potent in tissue from pregnant mice; explants from parous animals displayed intermediate sensitivity, suggesting that DNA structure was permanently altered. However, casein synthesis in glands from parous mice required hormone concentrations as high as in virgins and are just as susceptible to ethidium bromide as in virgins. Similarly, the vulnerability of the casein gene to DNAase I digestion is low in mammary epithelial cells from virgins, high in cells from pregnant mice, and low again in cells from parous animals. These data suggest that during the first pregnancy of mice, there are changes in the chromatin configuration that may facilitate the transcription of milk-related mRNA. Furthermore, after mammary gland involution these changes in the casein gene undergo reversion, while those involved with lactose synthetase activity persist; this may explain the disparate hormonal responsiveness seen in these animals with respect to casein and lactose synthesis.
Mol Cell Endocrinol 1984 May
PMID:Enhanced hormonal responsiveness in mammary glands from parous mice: molecular mechanisms. 620 88

The organ-culture technique was used to investigate the effects of lysomotropic agents (NH4Cl and chloroquine) and of modifiers of microfilaments (cytochalasin B) and microtubules (colchicine) on the induction of casein synthesis and the accumulation of casein mRNA by prolactin in the rabbit mammary gland. Neither chloroquine nor NH4Cl altered the lactogenic action of prolactin. Cytochalasin B attenuated the response to prolactin in terms of casein synthesis. However, this drug did not hamper the accumulation of casein mRNA. Colchicine exhibited a marked specific inhibitory effect on the induction of casein synthesis. It also prevented the accumulation of casein mRNA. These results suggest that a putative degradation of the internalized prolactin--receptor complex by lysosomes is not strictly involved in prolactin action. In addition, the integrity of the microfilaments seems unnecessary in the process of casein-gene activation by prolactin. By contrast, the integrity of the microtubule network seems absolutely necessary to ensure the transmission of prolactin information to the nucleus.
Mol Cell Endocrinol 1980 Jan
PMID:Effects of lysomotropic agents, and of microfilament- and microtubule-disrupting drugs on the activation of casein-gene expression by prolactin in the mammary gland. 624 4

Protein phosphatase, active on non-histone phosphoprotein substrate, was partially purified from rat liver cell nuclei by means of salt extraction, ammoniumsulfate precipitation, DEAE cellulose chromatography, gel filtration and preparative isoelectrofocusing. Rat liver nuclei contain a heterogenous population of different protein phosphatases. All the enzyme fractions eluted from DEAE cellulose are of low molecular weight between 12,000--31,000. The pH 5.5 peak fraction of preparative isoelectrofocusing was characterized in detail. It has a pH optimum of 6.8 using nuclear phosphoprotein substrate. It is inhibited by Na+ at 80 mM, and to a lesser extent by K+, activated by Mg2+ (5 mM) and Mn2+ (1 mM). However, the latter is inhibitory at 6 mM. The nuclear protein phosphatase is also active on labelled F1 and F2b histones and casein, however, its V is lower on histones and it contains component(s) active specifically on nuclear phosphoprotein substrate but not on casein.
Mol Cell Biochem 1980 Aug 29
PMID:Protein phosphatase from rat liver nuclei. 625 11

In vitro experiments were carried out in order to investigate the influence of Cu++-ions on the tryptic hydrolysis of casein and soybean protein. The admixture of 10(-3) to 10(-2) Mol Cu++/l to the reaction preparations results in the activation of trypsin in both substrates. The further increase of the Cu++-concentration results in a decrease of the trypsin activity and, with casein as substrate, in trypsin inhibition. The effects are similar with the synthetic substrate N alpha-benzoyl-L-arginine-p-nitroamilide (L-BAPA), however, trypsin is already activated after the admixture of approximately 5 x 10(-6) Mol Cu++/l. Since the admixture of Cu++-ions in experiments with pepsin in similar concentrations as with trypsin also results in an activation, the question is being discussed whether the improved protein digestibility and the higher weight increase of pigs which received 250 ppm copper can be traced back to these effects.
 ...
PMID:[Effect of Cu++ ions on the activity of trypsin on natural substance]. 626 18

Two key steroidogenic mitochondrial cytochromes P-450 (cholesterol side-chain cleavage (scc) and 11 beta-hydroxylation (11 beta)) were purified from bovine adrenal cortex and examined as potential phosphorylatable substrates using purified cAMP-dependent protein kinase subunit (C) and A type (CKA) and G type (CKG) cAMP-independent casein kinases. Of the two cytochromes P-450, only P-450 11 beta was able to incorporate phosphate from ATP in the presence of C (Km = 7.5 microM), whereas CKA and CKG were ineffective. Phosphorylation of P-450 11 beta (maximum incorporation of 1 mole of 32P per mole of cytochrome, only on serine residues) did not modify the enzymatic activity of an 11 beta-hydroxylation system reconstituted in vitro from purified components, when adrenodoxin was in excess in the reaction. However, kinetic studies showed that P-450 11 beta phosphorylation strikingly increases the P-450 11 beta-adrenodoxin affinity in a phosphorylation-dependent manner. This would result in a net increase in 11 beta-hydroxylase activity under in vivo conditions where adrenodoxin availability is limited. Possible significance of these observations in the regulation of differentiated adrenocortical functions remains to be further examined.
Mol Cell Endocrinol 1982 Jul
PMID:Phosphorylation of purified mitochondrial cytochromes P-450 (cholesterol desmolase and 11 beta-hydroxylase) from bovine adrenal cortex. 628 91

The cytosol fraction from rat midbrain was chromatographed on DEAE-cellulose with a linear NaCl gradient (0-0.3 M). Two peaks of protein kinase activity were obtained when assayed with either histone or casein. A similar elution profile of the kinase activity was obtained from rat heart. The first peaks from midbrain and heart were compared in terms of their dependency upon cAMP and sensitivity to the endogenous protein kinase inhibitor. Neither of the two substances had an effect on the activity of the brain kinase. Furthermore, the dissociability of the midbrain and heart enzymes in the presence of cAMP or histone was compared by DEAE-cellulose chromatography. The heart enzyme was dissociated into a catalytic subunit characteristic of a cAMP-dependent protein kinase, whereas the brain kinase was totally unaffected by the cAMP or histone. The results of these tests indicate that although the elution profiles from DEAE-cellulose are similar between midbrain and heart, the first peak from brain contains a protein kinase that appears to be cAMP independent.
Mol Cell Biochem 1982 Dec 10
PMID:Soluble protein kinase fractions from DEAE-cellulose chromatography. A comparison between brain and heart from the rat. 629 94

Cyclic AMP-independent protein kinases in cytosol from rat thyroid glands were evaluated using histone and casein as exogenous substrates. Compared with other rat tissues, thyroid gland is rich in histone kinases, while its casein kinase activity is lower than that of liver and brain. Thyroidal cAMP-independent protein kinases can be resolved by sucrose gradient ultracentrifugation into two distinct peaks of histone (HKi-1 and HKi-2) and two peaks of casein (CKi-1 and CKi-2) kinases. An intermediate peak of histone kinase activity is only occasionally present. The four main kinase peaks are distinct with respect to several properties: their sedimentation coefficients are significantly different; only one out of the four peaks (CKi-2) can use GTP as substrate; monovalent ions strongly inhibit (50%) light peaks (HKi-1 and CKi-1), while heavy peaks (HKi-2 and CKi-2) are slightly but significantly stimulated (30%); light peaks are very sensitive to thermal inactivation, while heavy peaks are much more resistant. Their reactivity to hormonal action is different: in chronically stimulated glands HKi-2 is selectively and strongly stimulated (240%) while CKi-1 is not changed. In human pathological tissues independent alterations in different kinase entities were observed compared with healthy tissue. In conclusion, the four thyroidal c-AMP-independent protein kinases resolved on sucrose gradient seem to represent distinct entities which are independently and selectively controlled by hormones, and specifically altered in human pathological tissues.
Mol Cell Endocrinol 1983 Feb
PMID:Some characteristics and hormonal control of thyroidal cAMP-independent protein kinases. 629 18

Phosphoprotein phosphatase was purified from swine kidney by chromatography on DEAE-Sephadex A-50, Sephacryl S-200 and Sepharose 4B columns containing covalently bound hexanediamine and polylysine. The enzyme was purified more than 20000-fold and the homogeneous preparation had a specific activity of 2.8 micromol per min per mg of protein with saturating concentrations of 32P-histone as the substrate. The phosphatase showed only a single protein band when examined by polyacrylamide gel electrophoresis and a single protein peak containing all of the enzymatic activity was observed during chromatography on Sephadex G-100 column. The molecular weight of the purified enzyme was determined to be 70000 +/- 5000 by exclusion chromatography on a calibrated Sephadex G-100 column. Similar values were obtained by sucrose density centrifugation, 70000 +/- 5000, and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, 70000 +/- 3000. The purified enzyme catalyzed the dephosphorylation of the phosphorylated forms of glycogen synthase, phosphorylase, histone, phosphofructokinase, Type II regulatory subunit of cyclic AMP-dependent protein kinase, casein and protamine. The apparent Km values for these substrates were 3.6 microM, 2.8 microM, 66 microM, 3.3 microM, 8.0 microM, 6.6 microM and 100 microM, respectively. The enzyme did not hydrolyze low molecular weight phosphate esters such as glucose 6-phosphate, glycerol phosphate, adenosine nucleotides and inorganic pyrophosphate. The activity of the enzyme towards a phosphorylated protein substrate was competitively inhibited by the addition of other substrates. These results suggest that swine kidney contains a phosphoprotein phosphatase with a rather broad substrate specificity for a number of endogenous and exogenous phosphoprotein substrates.
Mol Cell Biochem 1983
PMID:Purification and properties of swine kidney phosphoprotein phosphatase. 630 89

pp60v-src, the product of the Rous sarcoma virus src gene, was partially purified by immunoaffinity chromatography from extracts of Rous sarcoma virus-transformed field vole cells. Incubation of this preparation with ATP plus Mg2+ and subsequent repurification by chromatography on hexylamine-agarose resulted in a net increase in the specific activity of the src protein kinase. This increase in phosphotransferase activity was detected by using a variety of substrates including casein, tubulin, and a 34,000-dalton protein presumed to be an in vivo target substrate of pp60v-src. In all cases, the phosphorylation was at tyrosine residues, and the kinase activity was inhibited by preincubation of the enzyme with immunoglobulin G prepared from tumor-bearing rabbit sera. The implications of these results for the regulation and control of pp60v-src-associated kinase activity are discussed.
Mol Cell Biol 1983 Sep
PMID:Increase in the phosphotransferase specific activity of purified Rous sarcoma virus pp60v-src protein after incubation with ATP plus Mg2+. 631 23

Patterns of cAMP-dependent protein kinases and cAMP-independent histone and casein kinases of hyperplastic rat thyroid glands and of human nodular non-toxic goitres have been analysed in two subcellular compartments, cytosol and particulate fraction. In hyperplastic rat glands the different compartmentalization of the two cAMP-dependent isoenzymes was preserved and the pattern of cAMP-independent protein kinases was not changed qualitatively, but the activities of the three classes of protein kinases were enhanced to different degrees: the highest increase was observed for the cAMP-dependent enzymes and the lowest for the cAMP-independent casein kinases. Analysis of individual peaks of cAMP-dependent kinases showed selective stimulation of the cytosolic Type II form and independent control of the Type I activity in the two subcellular compartments. Among cAMP-independent protein kinases only two histone kinase peaks were selectively enhanced; other kinase entities were changed to a lesser degree. During the involution of hyperplastic glands, a transient but differential enhancement of nearly all kinases was noted at first, which was followed later by a strong decrease, more or less rapid, of almost all kinase activities. In the regressed glands, neither the thyroid weight nor the pattern of different kinase entities corresponded to those of control, untreated glands, indicating that some of the protein kinase alterations in hyperplastic tissues are partly irreversible. In spite of great similarities, human and rat goitre tissues are not identical. The most important difference was the loss of compartmentalization of the cAMP-dependent isoenzymes in human tissue. The different ratios of the light and heavy peaks of cytosolic cAMP-independent histone kinases was the second characteristic which distinguished human and rat glands.
Mol Cell Endocrinol 1983 Dec
PMID:Protein kinase patterns in hyperplastic rat thyroids and in human non-toxic nodular goitres. 631 84


<< Previous 1 2 3 4 5 6 7 8 9 10