Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin receptor (IR) and IGF-I receptor (IGF-IR) are structurally and functionally related and belong to the tyrosine kinase receptor family. In teleosti such as salmonids and turbot, occurrence of multiple IR and IGF-IR members has been reported, but the structures of a complete set of both IR and IGF-IR members in a single teleost species have not yet been characterized. In this study, we cloned and analysed four distinct cDNA clones for IR and IGF-IR members from the liver and kidney of the Japanese flounder (Paralichthys olivaceus). Deduced amino acid sequence analyses and phylogenetic analysis have revealed that two of them (fIR-1 and fIR-2) belong to IR members and the other two (fIGF-IR-1 and fIGF-IR-2) are IGF-IRs. fIR-1 and fIR-2 comprised 1369 and 1368 amino acid residues respectively, and fIGF-IR-1 and fIGF-IR-2 comprised 1412 and 1418 residues respectively. All the receptor proteins contained cysteine-rich domains in their alpha-subunits, and conserved each transmembrane and tyrosine kinase domains in their beta-subunits. The amino acid sequences of fIRs and fIGF-IRs showed more than 90% sequence identity with turbot IR and IGF-IR respectively. When compared with their mammalian homologues, fIGF-IR-1 and fIGF-IR-2 proteins contained large insertions at their C-termini, as was observed in the corresponding region of turbot IGF-IR. Occurrence of multiple species of mRNA for each IR and IGF-IR was suggested by Northern blot analyses. A ribonuclease protection assay revealed diverse expressions of four receptor mRNAs in a wide range of tissues including heart, liver, ovary, testis, brain, gill arch, kidney, skeletal muscle, intestine, stomach, spleen and eye of the flounder.
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PMID:Molecular cloning, identification and characterization of four distinct receptor subtypes for insulin and IGF-I in Japanese flounder, Paralichthys olivaceus. 1201 Jun 44

We calculated profiles for mean residue depth, contact order, and number of contacts in the native structure of a series of proteins for which folding has been studied extensively, the chymotrypsin inhibitor 2, the SH3 module from the src tyrosine kinase, the small ribonuclease barnase, the bacterial immunity protein Im7, and apomyoglobin. We compared these profiles with experimental data from equilibrium or pulse labeling hydrogen-deuterium exchange obtained from NMR and phi values obtained from the protein engineering approach. We find a good qualitative agreement between the hierarchy of formation of topological elements during the folding process and the ranking of secondary structure elements in terms of residue depth. Residues that are most deeply buried in the core of the native protein usually belong to stretches of secondary structure elements that are formed early in the folding pathway. Residue depth can thus provide a useful and simple tool for the design of folding experiments.
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PMID:The "first in-last out" hypothesis on protein folding revisited. 1602 37

Archival, formalin-fixed and paraffin-embedded tissues routinely stored in pathology departments represent an invaluable resource for retrospective molecular biology studies for diagnostic and prognostic purposes. In such specimens extraction of transcriptionally competent RNA to be analyzed by conventional techniques, such as reverse transcription-polymerase chain reaction, is a challenging task. Therefore, we developed a novel methodological approach that allows successful detection and semiquantitative analysis of specific mRNAs obtained from archival formalin-fixed, paraffin-embedded specimens by ribonuclease protection assay. Specifically, we measured a panel of 7 angiogenic markers in selected archival tissues stored at room temperature and retrieved over a wide time span (10 y). The study series consisted in samples of benign and malignant melanocytic lesions. In our model, expression of FLT-1, the vascular-endothelial growth factor receptor-1, correlated with the expression of mRNAs encoding other tyrosine kinase receptors, such as TIE-1 and TIE-2, as well as with angiopoietin and with the protease-activated receptor-1 and vascular-endothelial growth factor itself. Relative to control (normal skin), in melanoma the expression of the selected angiogenic markers was significantly higher. In conclusion, our study provides evidence that ribonuclease protection assay on archival specimens would be highly valuable for retrospective studies, for diagnosis or prognosis.
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PMID:A ribonuclease protection assay-based approach for analysis of angiogenic gene expression in archival tissues. 1772 22

The DNA damage response network stimulates microRNA (miRNA) biogenesis to coordinate repair, cell cycle checkpoints, and apoptosis. The multistep process of miRNA biogenesis involves the cleavage of primary miRNAs by the microprocessor complex composed of the ribonuclease Drosha and the RNA binding protein DGCR8. We found that the tyrosine kinase ABL phosphorylated DGCR8, a modification that was required for the induction of a subset of miRNAs after DNA damage. Focusing on the miR-34 family, ABL stimulated the production of miR-34c, but not miR-34a, through Drosha/DGCR8-dependent processing of primary miR-34c (pri-miR-34c). This miRNA-selective effect of ABL required the sequences flanking the precursor miR-34c (pre-miR-34c) stem-loop. In pri-miRNA processing, DGCR8 binds the pre-miR stem-loop and recruits Drosha to the miRNA. RNA cross-linking assays showed that DGCR8 and Drosha interacted with pri-miR-34c, but we found an inverse correlation between ABL-stimulated processing and DGCR8 association with pri-miR-34c. When coexpressed in HEK293T cells, ABL phosphorylated DGCR8 at Tyr(267). Ectopic expression of a Y267F-DGCR8 mutant reduced the recruitment of Drosha to pri-miR-34c and prevented ABL or Drosha from stimulating the processing of pri-miR-34c. In mice engineered to express a nuclear import-defective mutant of ABL, miR-34c, but not miR-34a, expression was reduced in the kidney, and apoptosis of the renal epithelial cells was impaired in response to cisplatin. These results reveal a new pathway in the DNA damage response wherein ABL-dependent tyrosine phosphorylation of DGCR8 stimulates the processing of selective primary miRNAs.
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PMID:The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage. 2612 15

The Microprocessor complex consisting of DROSHA (a type III ribonuclease) and DGCR8 (DiGeorge syndrome critical region gene 8-encoded RNA binding protein) recognizes and cleaves the precursor microRNA hairpin (pre-miRNA) from the primary microRNA transcript (pri-miRNA). The Abelson tyrosine kinase 1 (ABL) phosphorylates DGCR8 to stimulate the cleavage of a subset of pro-apoptotic pri-miRNAs, thus expanding the nuclear functions of ABL to include regulation of RNA processing.
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PMID:EnABLing microprocessor for apoptosis. 2718 51


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