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Biomedical subjects

M Yan

Publications and source records attributed to M Yan.

At least 91 records · Page 5Linked to original sources
PubMed1996

Raf, but not MEK or ERK, is sufficient for differentiation of hippocampal neuronal cells.

To elucidate signal transduction pathways leading to neuronal differentiation, we have investigated a conditionally immortalized cell line from rat hippocampal neurons (H19-7) that express a temperature sensitive simian virus 40 large T antigen. Treatment of H19-7 cells with the differentiating agent basic fibroblast growth factor at 39 degrees C, the nonpermissive temperature for T function, resulted in the activation of c-Raf-1, MEK, and mitogen-activated protein (MAP) kinases (ERK1 and -2). To evaluate the role of Raf-1 in neuronal cell differentiation, we stably transfected H19-7 cells with v-raf or an oncogenic human Raf-1-estrogen receptor fusion gene (deltaRaf-1:ER). deltaRaf-1:ER transfectants in the presence of estradiol for 1 to 2 days expressed a differentiation phenotype only at the nonpermissive temperature. However, extended exposure of the deltaRaf-1:ER transfectants to estradiol or stable expression of the v-raf construct yielded cells that extended processes at the permissive as well as the nonpermissive temperature, suggesting that cells expressing the large T antigen are capable of responding to the Raf differentiation signal. deltaRaf-1:ER, MEK, and MAP kinase activities in the deltaRaf-1:ER cells were elevated constitutively for up to 36 h of estradiol treatment at the permissive temperature. At the nonpermissive temperature, MEK and ERKs were activated to a significantly lesser extent, suggesting that prolonged MAP kinase activation may not be sufficient for differentiation. To test this possibility, H19-7 cells were transfected or microinjected with constitutively activated MEK. The results indicate that prolonged activation of MEK or MAP kinases (ERK1 and -2) is not sufficient for differentiation of H19-7 neuronal cells and raise the possibility that an alternative signaling pathway is required for differentiation of H19-7 cells by Raf.

Animals↗
PubMed1996

A three-step pathway of transcription initiation leading to promoter clearance at an activation RNA polymerase II promoter.

The progress of transcription bubbles during inhibition in vitro was followed in order to learn how RNA polymerase II begins transcription at the activated adenovirus E4 promoter. The issues addressed include the multiple roles of ATP, the potential effect of polymerase C-terminal domain phosphorylation, and the ability of polymerase to clear the promoter for reinitiation. The results lead to a three-step model for the transition from closed complex to elongation complex, two steps of which use ATP independently. In the first step, studied previously, ATP is hydrolyzed to open the DNA strands over the start site. In a second step, apparently independent of ATP, transcription bubbles move into the initial transcribed region where RNA synthesis can stall. In the third step, transcripts can be made as polymerase is released from these stalled positions with the assistance of an ATP-dependent process, likely phosphorylation of the polymerase C-terminal domain. After this third step, the promoter becomes cleared, allowing for the reinitiation of transcription.

Adenosine Triphosphate↗
PubMed1996

[A study on cAMP and Ca-CaM of the epithelium in human normal and cataractous lenses].

OBJECTIVE: The study was designed to study the relationship between calcium-calmodulin (Ca-CaM) and cyclic adenosine monophosphate (cAMP) systems and their possible cataractogenic effects. METHODS: We measured cAMP, Ca and Ca-CaM in the epithelium of human normal and cataractous lenses by enzymic and radioimmunoassay methods. RESULTS: The levels of Ca-CaM in the epithelium of senile cataractous lens were higher, while of cAMP were lower than that in the normal lens. CONCLUSION: The results imply that the low level of cAMP might cause the high level of calcium in the lens which is possibly a cataractogenic factor. The dangerous role of calcium is amplified by the elevation of Ca-CaM.

Adolescent↗
PubMed1995

Abortive initiation and first bond formation at an activated adenovirus E4 promoter.

Abortive initiation at the adenovirus E4 promoter was studied by following the production of RNA formed from the initiating nucleotides UpA and CTP. Formation of a specific short RNA via a reaction with appropriate alpha-amanitin sensitivity required promoter, activator, and ATP. In the absence of any of these, an alpha-amanitin-resistant reaction led to lower levels of a product of unknown origin. The alpha-amanitin-sensitive reaction required open promoter complexes, as assayed directly by permanganate probing. This reaction was not blocked by the inhibition of polymerase C-terminal domain kinase activity or by the lack of DNA supercoiling. Thus, formation of the initial bond of the mRNA appears to require activator and ATP to open the DNA but not phosphorylation of the polymerase C-terminal domain. In addition, the abortive initiation reaction was strongly suppressed when all elongation substrates were present, suggesting that cycling to produce high amounts of abortive product is strongly disfavored during productive initiation at this promoter.

Adenosine Triphosphate↗
PubMed1995

[Effects of glucocorticoid on PMN adhesion induced by TNF].

TNF was used as a stimulating factor to study the effects of glucocorticoid (GC) on polymorphonuclear leucocyte (PMN) adhesion. The results showed that tumor necrosis factor (TNF) could increase the PMN adhesion markedly, and Dex could not inhibit the PMN adhesion induced by TNF, but it had a certain effect of prevention. PMN adhesion was increased prominently when Dex and RU 38486 were given after TNF pretreatment.

Animals↗
PubMed1995

The analysis of disparity evoked potentials by a new form of static random-dot stereograms.

PURPOSE: A new form of static random-dot stereograms free of monocular clues was designed as stimulus to elicit disparity evoked potentials. METHODS: Disparity evoked potentials were recorded in 40 stereo-normal subjects. The stimulator was a white-black static random-dot stereograms generated by a computer and had no monocular clues. Every subject was tested in disparity stimulus, zero disparity stimulus, monocular stimulus and wearing prism condition. RESULTS: A characteristic wide positive wave at about 250 ms was consistently recorded in disparity stimulus, which may be regarded as evidence of the presence of stereopsis. In contrast, recordings for zero disparity stimulus, monocular vision, stimulus and wearing prism condition all demonstrated a markedly difference from recording for disparity stimulus.

Adolescent↗
PubMed1995

[Changes of intestinal flora in senile mouse models and the antagonistic activity of the root of Astragalus membraceus (Fisch) Bge].

Inhaled by mice, ozone induced stronger free radical reaction in the organism and led to a series of changes similar to senility. In this way the senility mouse models were established to observe the changes of intestinal flora in senile mice. The senile mice were given the root of Astrogolus membraceus decoction orally. The results showed that the imbalance of intestinal flora in these mice was recovered.

Aging↗
PubMed1994

Crystal structure of recombinant farnesyl diphosphate synthase at 2.6-A resolution.

The synthesis of farnesyl diphosphate (FPP), a key intermediate in the isoprenoid biosynthetic pathway required for the synthesis of cholesterol and in the formation of prenylated proteins, is catalyzed by the enzyme farnesyl diphosphate synthase (FPS). The crystal structure of avian recombinant FPS, the first three-dimensional structure for any prenyltransferase, was determined to 2.6-A resolution. The enzyme exhibits a novel fold composed entirely of alpha-helices joined by connecting loops. The enzyme's most prominent structural feature is the arrangement of 10 core helices around a large central cavity. Two aspartate-rich sequences that are highly conserved among the isoprenyl diphosphate synthase family of prenyltransferases, and are essential for enzymatic activity, were found on opposite walls of this cavity, with the aspartate side chains approximately 12 A apart and facing each other. The location and metal ion binding properties of these sequences suggest that the conserved aspartate residues participate in substrate binding of catalysis.

Alkyl and Aryl Transferases↗
PubMed1994

Identification of 2 serine residues of MEK-1 that are differentially phosphorylated during activation by raf and MEK kinase.

The signal transduction kinase MEK (mitogen-activated protein (MAP) or extracellular signal-regulated (Erk) kinase)-1 is activated via phosphorylation by MEKK (MEK kinase) and raf kinases. We show here that these two kinases phosphorylate rat MEK-1 exclusively on two serine codons, Ser218 and Ser222. Phosphorylation of MEK-1 on serines 218 and 222 is both necessary and sufficient for MEK-1 to be activated and able to phosphorylate MAP kinase. A mutant form of MEK-1 that replaces these two codons with alanine cannot be activated, and one that substitutes glutamic acid residues in place of these 2 serines is active independent of activation by phosphorylation. These sites of activation occur in a region of MEK-1 that is similar to sites of activating phosphorylation in several other serine/threonine kinases, suggesting that this region may represent a conserved "activating domain" of many kinases. MEKK and raf display differences in site preference between these two codons, with MEKK showing preference for the amino acid at codon 218 and raf phosphorylating each residue approximately equally. This site preference might result in differences in the temporal or subsequent substrate patterns of MEK activation that result from these two activation pathways.

Amino Acid Sequence↗