Casein Kinase Iγ Subfamily Zhai, Lanmin; Graves, Paul R.; Robinson, Lucy C. ...
The Journal of biological chemistry,
05/1995, Letnik:
270, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Casein kinase I, one of the first protein kinases identified biochemically, is known to exist in multiple isoforms in mammals. Using a partial cDNA fragment corresponding to an isoform termed CK1γ, ...three full-length rat testis cDNAs were cloned that defined three separate members of this subfamily. The isoforms, designated CK1γ1, CK1γ2, and CK1γ3, have predicted molecular masses of 43,000, 45,500, and 49,700. CK1γ3 may also exist in an alternatively spliced form. The proteins are more than 90% identical to each other within the protein kinase domain but only 51-59% identical to other casein kinase I isoforms within this region. Messages for CK1γ1 (2 kilobases (kb)), CK1γ2 (1.5 and 2.4 kb), and CK1γ3 (2.8 kb) were detected by Northern hybridization of testis RNA. Message for CK1γ3 was also observed in brain, heart, kidney, lung, liver, and muscle whereas CK1γ1 and CK1γ2 messages were restricted to testis. All three CK1γ isoforms were expressed as active enzymes in Escherichia coli and partially purified. The enzymes phosphorylated typical in vitro casein kinase I substrates such as casein, phosvitin, and a synthetic peptide, D4. Phosphorylation of the D4 peptide was activated by heparin whereas phosphorylation of the protein substrates was inhibited. The known casein kinase I inhibitor CK1-7 also inhibited the CK1γs although less effectively than the CK1α or CK1δ isoforms. All three CK1γs underwent autophosphorylation when incubated with ATP and Mg2+. The YCK1 and YCK2 genes in Saccharomyces cerevisiae encode casein kinase I homologs, defects in which lead to aberrant morphology and growth arrest. Expression of mammalian CK1γ1 or CK1γ3 restored growth and normal morphology to a yeast mutant carrying a disruption of YCK1 and a temperature-sensitive allele of YCK2, suggesting overlap of function between the yeast Yck proteins and these CK1 isoforms.
Casein Kinase I Subfamily Lanmin Zhai; Paul R. Graves; Lucy C. Robinson ...
The Journal of biological chemistry,
05/1995, Letnik:
270, Številka:
21
Journal Article
Recenzirano
Casein kinase I, one of the first protein kinases identified biochemically, is known to exist in multiple isoforms in mammals.
Using a partial cDNA fragment corresponding to an isoform termed CK1 , ...three full-length rat testis cDNAs were cloned that defined three separate members of this subfamily. The isoforms, designated
CK1 1, CK1 2, and CK1 3, have predicted molecular masses of 43,000, 45,500, and 49,700. CK1 3 may also exist in an alternatively spliced form. The proteins are more than 90% identical to each other within the protein
kinase domain but only 51-59% identical to other casein kinase I isoforms within this region. Messages for CK1 1 (2 kilobases (kb)), CK1 2 (1.5 and 2.4 kb), and CK1 3 (2.8 kb) were detected by Northern hybridization of testis RNA. Message for CK1 3 was also observed in brain, heart, kidney, lung, liver, and muscle whereas CK1 1 and CK1 2 messages were restricted to testis. All three CK1 isoforms were expressed as active enzymes in Escherichia coli and partially purified. The enzymes phosphorylated typical in vitro casein kinase I substrates such as casein, phosvitin, and a synthetic peptide, D4. Phosphorylation of the D4 peptide was
activated by heparin whereas phosphorylation of the protein substrates was inhibited. The known casein kinase I inhibitor
CK1-7 also inhibited the CK1 s although less effectively than the CK1α or CK1 isoforms. All three CK1 s underwent autophosphorylation when incubated with ATP and Mg . The YCK1 and YCK2 genes in Saccharomyces cerevisiae encode casein kinase I homologs, defects in which lead to aberrant morphology and growth arrest. Expression of mammalian
CK1 1 or CK1 3 restored growth and normal morphology to a yeast mutant carrying a disruption of YCK1 and a temperature-sensitive allele of YCK2 , suggesting overlap of function between the yeast Yck proteins and these CK1 isoforms.
Synthetic bovine parathyroid hormone containing the 1-34 NH2-terminal amino acids bPTH-(1-34) inhibits uterine contraction stimulated by a variety of agonists. Previously, we reported that the ...parathyroid hormone analogue Nle8, Nle18, Tyr34bPTH-(3-34)amide NTA-(3-34) antagonized this effect of bPTH-(1-34) while the analogue Tyr34bPTH-(7-34)amide bPTH-(7-34) used in this study stimulated uterine contraction. However, contrary to this previous report, bPTH-(7-34) in the present study failed to initiate a contractile response and instead resulted in an inhibitory response to the bPTH-(1-34) effect on uterine contraction in a dose-related manner. The inhibitory response of bPTH-(7-34) was further confirmed by demonstrating that this preparation of bPTH-(7-34) was capable of blocking bPTH-(1-34)-stimulated adenylate cyclase activity on particulate fractions of osteoblast-like cells from neonatal mouse calvarial. These results are consistent with those in the literature for the antagonistic effect of the 7-34 PTH fragment.
Substantial progress has been made in eradicating the boll weevil from the majority of the cotton producing regions in Texas. While the full economic benefits will not be realized until eradication ...is achieved statewide, economic benefits approaching $1 billion have already been realized.
Gonadotropin-releasing hormone (GnRH) tests (12 women) and estradiol benzoate stimulation tests (8 women) were carried out before and during short- or long-term treatment with danazol. There was no ...difference in the height or timing of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) peaks following GnRH or estradiol benzoate between any of the treatment groups or between the pretreatment and treatment responses within groups. However, some individuals did show an apparent attenuation of response during treatment.
These results indicate that danazol does not produce a profound or consistent suppression of the hypothalamus or pituitary in normal women in the reproductive age group. The impressive clinical effect of danazol may be mediated by additive minor to moderate suppressive effects at each level of the hypothalamic-pituitary-ovarian-endometrial axis.
Eight subjects with normal menstrual cycles were treated with danazol (800 mg daily) during one luteal phase to assess the effect on follicular development in the subsequent cycle. Plasma levels of ...luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone were measured daily throughout both cycles. Following danazol there was a consistent and significant delay to the preovulatory estradiol (P < 0.05) and LH (P < 0.02) peaks and a significant suppression of the early follicular phase FSH (P < 0.05) and preovulatory estradiol peak plasma levels (P < 0.05). All other parameters of the post-danazol cycle were indistinguishable from normal. However, there was a small suppression of midluteal phase FSH during danazol treatment, compared with the posttreatment cycle, which was significant for three subjects. It is suggested that the small effect of luteal phase danazol on subsequent follicle development may occur at an intraovarian level through an effect on receptors or enzymes as well as through the small degree of suppression of midluteal phase and early follicular phase FSH.
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