Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammary tissue (4 x 4 x .3 mm) from five cows was placed subcutaneously in ovariectomized athymic nude mice. After 30 d mice were injected daily for 20 d with saline (controls), 17 beta-estradiol (1 microgram), progesterone (1 mg), or estradiol plus progesterone. Deoxyrobonucleic acid synthesis of bovine ductal epithelium was increased by estradiol, progesterone, or both. Cyclic 3',5'-adenosine monophosphate concentration of bovine mammary grafts was also increased by estradiol or progesterone. Estradiol increased cyclic 3',5'-adenosine monophosphate-dependent protein kinase activity and decreased cyclic 3',5'-guanosine monophosphate concentration in bovine mammary tissue. Progesterone decreased cyclic 3',5'-guanosine monophosphate-dependent protein kinase activity of bovine mammary tissue. In a second experiment, athymic nude mice bearing mammary tissue from five cows first received 20 d of pretreatment with saline or estradiol plus progesterone. Mice were then injected with saline or hydrocortisone (.2 mg/d) plus bovine prolactin (1 mg/d) for 2 d. Hydrocortisone plus prolactin enhanced alpha-lactalbumin production by bovine mammary tissue and had a greater effect in mice that had received estradiol plus progesterone. Pretreatment with estrogen plus progesterone increased tissue cyclic 3',5'-adenosine and monophosphate and cyclic 3',5'-adenosine monophosphate-dependent protein kinase and decreased cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-guanosine monophosphate-dependent protein kinase. In mice that received estradiol plus progesterone, treatment with hydrocortisone plus prolactin decreased bovine mammary tissue cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-adenosine monophosphate-dependent protein kinase but increased tissue cyclic 3',5'-guanosine monophosphate-dependent protein kinase.
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PMID:Cyclic nucleotide concentrations and protein kinase activities of bovine mammary tissue maintained in athymic nude mice: effects of mammogenic and lactogenic hormones. 283 85

Incubation of cultured ovine pituitary cells with the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) (0.1-100 nM), caused a dose-related stimulation of both growth hormone (ED50 approximately 4 nM) and prolactin (ED50 approximately 14 nM) secretion. Stimulation by TPA (100 nM) produced a substantial 10-fold increase in growth hormone with a smaller, 2-fold rise in prolactin secretion over 30 min; significant effects on the release of both hormones occurred within 2 min. Treatment with TPA also produced a small, time- and concentration-dependent rise in cellular cyclic AMP content which reached, at maximum, a level 20-30% over basal values. Non-tumor-promoting phorbol esters did not stimulate the secretion of either growth hormone or prolactin. In the presence of TPA (10 nM), dopamine (1-1000 nM) suppressed prolactin secretion to a level close to that observed for maximal inhibition of unstimulated cells. At high concentrations (0.1-1.0 microM) dopamine also partially attenuated (by 43%) the TPA-induced stimulation of growth hormone secretion. Somatostatin (0.01-1.0 microM) completely inhibited the substantial (approximately 9-fold) TPA-induced stimulation of growth hormone secretion (inhibitory ED50 approximately 47 nM), and also suppressed TPA-stimulated prolactin secretion to the control level. Our results suggest that activation of protein kinase-C may be involved in the stimulatory regulation of both growth hormone and prolactin secretion in sheep pituitary cells. Failure of TPA to attenuate the inhibitory activity of dopamine and somatostatin suggests that inhibitory regulation occurs at, or beyond, the point in the secretory process regulated by protein kinase-C.
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PMID:Effects of dopamine and somatostatin on phorbol ester-stimulated prolactin and growth hormone secretion. 287 53

The existence of two cyclic nucleotide-independent protein kinases in the cytosolic extract of mouse mammary gland has been determined via DEAE-cellulose and Sephacryl column chromatography. Both enzymes phosphorylated casein in the absence of the exogenous cyclic nucleotides, cAMP and cGMP. One protein kinase was found to have a molecular weight of approx. 30 000, while the other was found to have a molecular weight in the range 150 000-250 000. The activity of the larger species was enhanced by polyamines and inhibited by heparin. This enzyme utilized both ATP and GTP as phosphate donors; the apparent Km values were 10 and 16 microM, respectively. The lower molecular weight protein kinase was not affected by either polyamines or heparin and utilized only ATP (Km = 8 microM) as the phosphate donor. The polyamine-responsive protein kinase activity in the mammary gland varied as a function of the reproductive development of the mouse. The activity was relatively low in the virgin and primiparous stages, increased during pregnancy and peaked during lactation. Studies using mammary organ culture indicated that the combination of insulin (5 micrograms/ml), cortisol (1 micrograms/ml) and prolactin (5 micrograms/ml) maintained the polyamine-responsive protein kinase activity that was present in noncultured tissue. In the absence of prolactin, however, the kinase activity was significantly lower than that observed in the three-hormone system. When dibutyryl cyclic AMP (0.5 mM) was added to the medium along with the three hormones, a significant decrease in enzyme activity was found. Slab gel electrophoresis and autoradiography showed that the majority of the phosphorylated endogenous substrates in the cytosolic fraction were caseins. The results of this study suggest that the polyamine-responsive protein kinase may play an important role in the growth and development of the mammary gland.
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PMID:The characterization and regulation of a polyamine-responsive, cyclic nucleotide-independent protein kinase activity in the mouse mammary gland. 298 27

In experiments designed to study the mechanism by which peptide hormones binding to their plasma membrane receptors stimulate the expression of specific genes, the transcription of two neuroendocrine genes, prolactin and growth hormone, was analyzed in a rat pituitary cell line. The results showed that cyclic adenosine monophosphate (cyclic AMP) stimulates the transcription of discrete subsets of eukaryotic genes by at least two independent molecular mechanisms. Cyclic AMP stimulated growth hormone gene transcription and phosphorylation of a 19,000-dalton nuclear protein; this appears to reflect direct nuclear actions of the cyclic AMP-dependent protein kinase. In contrast, the stimulation by cyclic AMP of prolactin gene transcription appears to reflect activation of a discrete calcium-dependent event.
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PMID:Cyclic AMP regulation of eukaryotic gene transcription by two discrete molecular mechanisms. 299 47

By comparing the 5'-flanking region of the porcine gene for the urokinase form of plasminogen activator with those of other cAMP-regulated genes, we identify a 29-nucleotide sequence that is tentatively proposed as the cAMP-regulatory unit. Homologous sequences are present (i) in the cAMP-regulated rat tyrosine aminotransferase, prolactin, and phosphoenolpyruvate carboxykinase genes and (ii) 5' to the transcription initiation sites of cAMP-regulated Escherichia coli genes. From this we conclude that the expression of cAMP-responsive genes in higher eukaryotes may be controlled, as in E. coli, by proteins that form complexes with cAMP and then show sequence-specific DNA-binding properties. The complex formed by cAMP and the regulatory subunit of the type II mammalian protein kinase might be one candidate for this function. Based on several homologies we suggest that this subunit may have retained both the DNA-binding specificity and transcription-regulating properties in addition to the nucleotide-binding domains of the bacterial cAMP-binding protein. If this were so, dissociation of protein kinase by cAMP would activate two processes: (i) protein phosphorylation by the catalytic subunit and (ii) transcription regulation by the regulatory subunit.
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PMID:Gene expression and cAMP. 299 82

DMBA induced rat mammary tumors were used to study the association of tyrosine protein kinase activity with tumor growth. Pharmacological manipulations of blood prolactin level, by perphenazine and bromocriptine, were used to stimulate or arrest tumor growth, respectively. During perphenazine treatment, a 2-3-fold increase in membranal tyrosine protein kinase activity, measured with angiotensin II as substrate, preceded the 3-4-fold increase in tumor area. At the same time the cAMP-dependent protein kinase activity, measured with kemptide as substrate, did not change.
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PMID:Membranal tyrosine protein kinase activity (but not cAMP-dependent protein kinase activity) is associated with growth of rat mammary tumors. 299 29

Rat prolactin exhibits microheterogeneity when examined in electrophoretic systems, running as three isoforms having the same molecular weight but different net charges (prolactins 1, 2, and 3 with isoform 3 being the most acidic). As there is precedent for the phosphorylation of a pituitary hormone and phosphorylation is a common cause of microheterogeneity, we examined the possibility that rat prolactin existed in differentially phosphorylated forms. The investigation included examinations of rat prolactin phosphorylation both in vitro and in vivo. For the in vitro studies, purified rat prolactin was incubated with [gamma-32P]ATP and low levels of each of five purified protein kinases. Phosphorylated rat prolactin was identified by autoradiography of silver-stained one- and two-dimensional gels. For the in vivo studies, rat anterior pituitary cells in primary culture were incubated in the presence of H3 32PO4 for 2 or 12 h, after which time the proteins were extracted from the cells, cold acetone-precipitated, or immunoprecipitated and run on two-dimensional gels. We report the in vitro phosphorylation of rat prolactin by cAMP-dependent protein kinase, casein kinase I, protease-activated kinase I, and the calcium/phospholipid-dependent kinase, that phosphorylation with these kinases results in phosphate incorporation only into isoforms 2 and 3, and the phosphorylation of prolactin in rat pituitary cells in primary culture.
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PMID:Phosphorylation of prolactin. 300 80

The purpose of this study was to characterize the action of phorbol 12-myristate 13-acetate (PMA), a tumor-promoting agent, on rat anterior pituitary gland, focusing the attention on prolactin secretion. PMA elicited a significant increase in prolactin secretion without affecting phosphatidylinositol turnover, considered as an early post-receptor event controlling PRL secretion. However incubation of anterior pituitary glands with PMA caused a loss of protein kinase-C activity in cytoplasm concomitant with an increased enzyme activity in the membrane. The action of PMA on prolactin secretion seems to be mainly dependent from the redistribution and activation of protein kinase-C. In fact, the phorbol ester did not affect pituitary cAMP and cGMP metabolism either in basal conditions or after theophylline.
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PMID:Phorbol 12-myristate 13-acetate induces prolactin secretion from rat anterior pituitary gland by the activation of protein kinase-C. 309 41

The synthesis and phosphorylation of H1 histones were studied in organ cultures of midpregnant mouse mammary glands exposed to various combinations of insulin, cortisol and prolactin over a 48-h period. The synthesis of specific H1 histone subtypes was changed only when all three hormones were present, and the effect was most pronounced during the first 24 h of culture, a period of cell replication. The 3-hormone combination also stimulated the phosphorylation of the N-terminal region of the H1 histone, and this also occurred maximally during the first 24 h of culture. The enhanced phosphorylation of the N-terminal region of the H1 histone included a site sensitive to phosphorylation by cyclic AMP-dependent protein kinase. Thus, hormones which stimulate mammary development in vitro influence the synthesis and specific phosphorylation of H1 histones during a period of cell replication preceding the expression of milk protein genes.
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PMID:H1 histone synthesis and phosphorylation in mouse mammary gland in vitro. 331 80

Despite the extensive literature on the biological actions of Ca2+ and calmodulin, very little is known about their involvement in nuclear functions, e.g., regulation of specific gene expression. To date, the only genes other than prolactin and growth hormone shown to be regulated by perturbations in cell Ca2+ are those coding for two glucose-regulated proteins. However, there is a growing body of indirect evidence for nuclear functions of Ca2+ and calmodulin, and we suspect that other examples of Ca2+-regulated genes will emerge. We have described in this chapter several different experimental approaches which we have employed to examine first whether prolactin gene expression is regulated by changes in cell Ca2+ content, and then to begin searching for the components of the mechanism by which Ca2+ exerts its effects on the prolactin gene. The tentative identification of 56-kDa nuclear matrix protein as both a calmodulin-binding protein and a substrate of a Ca2+-calmodulin-dependent protein kinase suggests that NMP 56 may be a subunit of a multifunctional Ca2+-calmodulin-protein kinase. This enzyme was recently detected in the nuclear matrix fraction of neuronal nuclei, and was shown to phosphorylate a chromatin protein similar to high mobility group protein 17 (HMG 17). Since HMG 17 is associated with actively transcribed chromatin, its phosphorylation in GH3 cells might play a role in the Ca2+-calmodulin-dependent regulation of prolactin gene expression by hormones and growth factors.
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PMID:Ca2+/calmodulin regulation of prolactin gene expression. 358 41


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