Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short-term exposure to okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, induced resumption of meiosis, including metaphase spindle formation, in mouse oocytes treated with a phosphodiesterase inhibitor, while long incubations with OA arrested oocyte maturation at a step prior to spindle formation. To explore the basis for this difference, the overall patterns of protein synthesis and phosphorylation and the production of tissue-type plasminogen activator (tPA), the synthesis of which is induced after germinal vesicle breakdown (GVBD), were analyzed under various OA treatments. Short-term exposure to OA led to tPA production and did not greatly affect the maturation-associated changes in protein phosphorylation. By contrast, a long application of OA did not result in tPA production and induced more marked changes in protein phosphorylation. Microinjection into prophase oocytes of the product of the fission yeast gene p13suc1, known to inhibit p34cdc2 kinase activation and/or activity, prevented meiotic reinitiation. This effect was overcome by microinjection of OA, at concentrations higher than those required for induction of maturation in the absence of p13suc1. These observations suggest that inhibition of phosphatase 1 or 2A or both triggers meiotic resumption by acting at the same site or at a site proximal to the p13suc1-sensitive step of cdc2 kinase activation.
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PMID:Okadaic acid and p13suc1 modulate the reinitiation of meiosis in mouse oocytes. 133 41

The B10/B10.A congenic mouse pair serves as a model for identifying specific genes related to morphogenesis and dysmorphogenesis of the embryonic palate and other organs. The present report describes our initial investigation of the Fraser-Juriloff paradigm, which proposes that susceptibility to malformation results from genetically determined differences in normal developmental patterns. Specifically, we evaluated the relationship between Igf2r gene expression, transforming growth factor-beta (TGF-beta) activation, and cdk4 gene expression. By using in situ hybridization, RNase protection assays, indirect immunofluorescence, Western blots, and bioassays, we show 1) the presence of insulin-like growth factor II (IGF-II), IGF-II receptor (IGF-IIR), IGF-IR, TGF-beta, plasminogen, plasminogen activators [urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA)], and Cdk4 in developing palates; 2) on embryonic day 14 (E14), which is a critical day for palatal growth, B10.A embryos have 82% greater IGF-IIR mRNA than B10; 3) on E14, B10.A embryonic palates have a 57% greater level of active TGF-beta2 than B10, although the total TGF-beta2 is nearly identical; and 4) on E14, B10 embryonic palates have a 52% greater level of Cdk4 mRNA than B10.A palates, a measure of cell cycle progression. Because cellular activation of latent TGF-beta appears to require binding to the mannose-6-phosphate (M6P) binding site of the IGF-IIR and is plasmin and plasminogen activator dependent, the positive correlation of IGF-IIR levels and active TGF-beta2 levels seems to be key. Thus, the strain variation of TGF-beta2/IGF-IIR-mediated growth inhibition in late G1 phase would appear to account for the slower growth and development of B10.A palates relative to B10. Elevated corticosteroid (CORT) exposure in E14 B10.A embryos significantly increases TGF-beta levels, 87% of which is TGF-beta2, as well as the levels of active TGF-beta, 64% of which is TGF-beta2. Without exogenous CORT, B10.A embryos do not have clefts; hence, we present an outline of pathogenesis: slower growing B10.A embryos have an up-regulation of IGF-IIR, which serves to sequester IGF-II from the growth-promoting IGF-IR and to bind more CORT-up-regulated, latent TGF-beta2 for subsequent plasmin-dependent activation; higher levels of TGF-beta2 signaling down-regulate Cdk4 and result in greater palatal growth inhibition at a critical stage of palatogenesis and, thus, cleft palate. We present an epigenetic model of information processing related to cell proliferation. The model is a dynamical network that uses continuous logic to learn its rules from changing conditions.
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PMID:Insulin-like growth factor II receptor, transforming growth factor-beta, and Cdk4 expression and the developmental epigenetics of mouse palate morphogenesis and dysmorphogenesis. 943 20

BACKGROUND: Prognostic factors for predicting the recurrence of node-negativebreast cancers have been controversial. The present study was performed to elucidate practically useful prognostic factors using formalin-fixed paraffin sections. METHODS: This was a case-controlled multi-institutional study that composed 40 patients with recurrent node-negative breast cancer and 80 patients with node-negative breast cancer but without recurrence after radical surgery. Tumors weresmaller than 3 cm in diameter and were treated surgically between January 1, 1985 and December 31, 1990. The recurrent and non-recurrent cases were matched with regard to their age, adjuvant chemotherapy and the year in which surgery was performed. Fourteen immunohistochemical factors and 8 histological factors of theprimary tumor were studied on formalin-fixed, paraffin-embedded sections by immunohistochemical and histochemical analyses. RESULTS: According to univariate analysis, factors such as progesterone receptor (PgR), MIB-1, CD44v6, CD44v9 and platelet-derived endothelial cell growth factor (PDECGF) were significantly different between the recurrent and non-recurrent groups (p &ly; 0.1; Wilcoxon-Mann-Whitney analysis). Chi-squared test showed significant differences in MIB-1, cdc2 and stromal plasminogen activator receptor (suPAR). Histologically, mitotic count was also significantly different between the two groups (p < 0.005). Multivariate analysis revealed that positivity for cdc2 (p=0.01), high mitotic count (p=0.04) and negativity for CD44v9 (p=0.02)were independent prognostic factors among variables selected by univariate analysis, and that positivity for MIB-1 (p=0.03) and cdc2 (p =0.01), and negativity for CD44v9 (p =0.03) were independent prognostic factors among the immunohistochemical markers examined. CONCLUSION: Our results indicated that positivity for MIB-1 and cdc2, high mitotic count and negativity for CD44v9 could serve as independent factors for predicting the recurrence of node-negative breast cancer.
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PMID:Prognostic Factors for Node-negative Breast Cancers: Results of a Study Program by the Japanese Breast Cancer Society. 1109 54