Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferin (PLF) is a secreted glycoprotein in the prolactin-growth hormone family in mice. PLF expression was detected in C3H 10T1/2 fibroblasts, but not in two 10T1/2-derived myogenic cell lines, and was restored in two nondifferentiating variants of one of these myogenic cell lines. Transient expression of one form of PLF (PLF1) inhibited expression from a muscle-specific gene promoter; a second form of PLF, which differed at three amino acid residues, displayed no activity in this transient assay. Introduction of a PLF1 expression construct into both muscle- and 10T1/2-derived myoblasts resulted in cell lines that were no longer myogenic or that differentiated only partially. Analysis of these cell lines revealed that differentiation could be obstructed at several steps and by one or more factors in addition to PLF. Although expected to function in vivo as an extracellular hormone, PLF did not appear to be acting through a cell surface receptor to inhibit differentiation in these cultured myoblasts.
Mol Cell Biol 1989 Feb
PMID:Participation of multiple factors, including proliferin, in the inhibition of myogenic differentiation. 246 1

When intact [3H]inositol-loaded turkey erythrocytes were stimulated with the purinergic agonist ADP, there was a rapid increase (2.5-fold after 30 sec) in the intracellular content of [3H]inositol 1,4,5-trisphosphate, followed by increases in the levels of [3H]inositol bisphosphate and [3H]inositol 1,3,4,5-tetrakisphosphate (4-fold and 5-fold, respectively, after 3 min). [3H]inositol monophosphate levels did not rise in the first 3 min of ADP stimulation but increased slowly thereafter, demonstrating that the primary response of turkey erythrocytes to purinergic stimulation is hydrolysis of phosphatidylinositol 4,5-bisphosphate. Inositol phosphate accumulation was evoked by a P2y purinoceptor, as indicated by the rank order of potencies of a variety of purinergic agonists. 2-Methylthioadenosine 5'-triphosphate was the most potent agonist tested, with an EC50 value of 0.36 microM. High performance liquid chromatography analysis demonstrated the presence of three distinct inositol tetrakisphosphate isomers in [3H]inositol-loaded turkey erythrocytes, inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,5)P4], inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,6)P4], and inositol 3,4,5,6-tetrakisphosphate. Prolonged stimulation with adenosine 5'-O-(2-thiodiphosphate), a nonhydrolyzable analogue of ADP, resulted in a 60-fold increase in the level of [3H]Ins(1,3,4,5)P4, whereas a substantial rise in the [3H]Ins(1,3,4,6)P4 fraction was also seen. These results indicate that turkey erythrocytes represent a valuable model system for studies of purinoceptor function as well as fundamental aspects of cell surface receptor-regulated phosphoinositide metabolism.
Mol Pharmacol 1989 Apr
PMID:Phosphatidylinositol 4,5-bisphosphate hydrolysis in turkey erythrocytes is regulated by P2y purinoceptors. 253 59

Nuclear uptake of 125I-labeled nerve growth factor (NGF) by cells that either express or do not express the cell surface receptor was tested using intact cells and a cell-free system. Intracellular and consequently nuclear uptake of NGF in intact cells was dependent on the presence of surface NGF receptor, whereas nuclear uptake in a cell-free system did not correlate with cell surface receptor expression. In the cell-free system, nuclear transport was inhibited when NGF receptor was being actively synthesized. Preincubation of intact cells with unlabeled NGF, cycloheximide, puromycin, or actinomycin D increased nuclear uptake up to threefold. The data suggest that, in intact cells, NGF transported into the cell via the surface receptors is also bound by the NGF receptor being synthesized in the cytoplasm. NGF taken up by the nucleus inhibited transcription of ribosomal RNA genes by 70% and, in turn, inhibited cell proliferation by 60%. A direct effect of NGF on transcription is discussed.
Mol Carcinog 1989
PMID:Intracellular receptor binding and nuclear transport of nerve growth factor in intact cells and a cell-free system. 254 27

Transcription of the low-density lipoprotein receptor (LDL-R) gene in the human monocytic leukemic cell line THP-1 and in the human hepatocarcinoma cell line Hep-G2 is regulated by second messengers of the diacylglycerol-protein kinase C (DAG-PKC), inositol 1,4,5-triphosphate-Ca2+, and cyclic AMP pathways. Exogenous phospholipase C (which releases DAG and inositol 1,4,5-triphosphate), PKC activators (phorbol esters and DAG), Ca2+ ionophores, and a cyclic AMP analog all transiently induced accumulation of LDL-R mRNA. The effects of these three signal-transducing pathways were to a large extent additive. Furthermore, PKC stimulation effected an increase in LDL binding, which suggested that the increase in LDL-R mRNA resulted in an increase in functional cell surface receptor activity. These results suggest that uptake of cholesterol by these cells is under control of both intracellular cholesterol levels and external signals.
Mol Cell Biol 1989 Jun
PMID:Involvement of second messengers in regulation of the low-density lipoprotein receptor gene. 254 77

We have previously shown that the developmentally regulated gene D2 is induced during aggregation by pulses of cAMP, which act via the cell surface receptor and consequent signal transduction pathways (W. Rowekamp and R.A. Firtel, 1980, Dev. Biol. 79, 409-418; S.K.O. Mann and R.A. Firtel, 1987, Mol. Cell. Biol. 7, 458-469; S.K.O. Mann, C. Pinko, and R.A. Firtel, 1988, Dev. Biol., in press). In this manuscript, we compare the complete derived amino acid sequence for D2 to two cloned and sequenced eukaryotic esterases and examine the requirement of the D2 gene product for development. Amino acid sequence data comparisons suggest that D2 encodes a serine esterase with strong sequence identity to Torpedo acetylcholine esterase and a Drosophila esterase. The protein has a putative leader sequence, suggesting that it is shunted into vesicles. Using an antisense gene construct driven by a Discoidin I promoter, whose transcriptional activity depends on the growth conditions of the cells, we show that inhibition of D2 mRNA accumulation results in an abnormal developmental program that includes the absence of normal streaming and incomplete aggregate formation and subsequent development. We suggest that D2 encodes an esterase function required for proper aggregation and subsequent development.
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PMID:Molecular analysis of a developmentally regulated gene required for Dictyostelium aggregation. 290 7

Molecular analysis of the human trk oncogene, a transforming gene isolated from a colon carcinoma biopsy, revealed the existence of a novel member of the tyrosine kinase gene family. This locus, which we now designate the trk proto-oncogene, codes for a protein of 790 amino acid residues that has several features characteristic of cell surface receptors. They include (i) a 32-amino-acid-long putative signal peptide, (ii) an amino-terminal moiety (residues 33 to 407) rich in consensus sites for N-glycosylation, (iii) a transmembrane domain, (iv) a kinase catalytic region highly related to that of other tyrosine kinases, and (v) a very short (15 residue) carboxy-terminal tail. Residues 1 to 392 were absent in the trk oncogene, as they were replaced by tropomyosin sequences. However, no other differences were found between the transforming and nontransforming trk alleles (residues 392 to 790), suggesting that no additional mutations are required to activate the transforming potential of this gene. The human trk proto-oncogene codes for a 140,000-dalton glycoprotein, designated gp140proto-trk. However, its primary translational product is a 110,000-dalton glycoprotein which becomes immediately glycosylated, presumably during its translocation into the endoplasmic reticulum. This molecule, designated gp110proto-trk, is further glycosylated to yield the mature form, gp140proto-trk. Both gp110proto-trk and gp140proto-trk proteins possess in vitro kinase activity specific for tyrosine residues. Finally, iodination of intact NIH 3T3 cells expressing trk proto-oncogene products indicated that only the mature form, gp140proto-trk, cross the plasma membrane, becoming exposed to the outside of the cell. These results indicate that the product of the human trk locus is a novel tyrosine kinase cell surface receptor for an as yet unknown ligand.
Mol Cell Biol 1989 Jan
PMID:Molecular and biochemical characterization of the human trk proto-oncogene. 292 93

Extracellular molecules regulate gene expression in eucaryotes. Exogenous cyclic AMP (cAMP) affects the expression of a large number of developmentally regulated genes in Dictyostelium discoideum. Here, we determine the specificity of the receptor(s) which mediates gene expression by using analogs of cAMP. The order of potency with which these analogs affect the expression of specific genes is consistent with the specificity of their binding to a cell surface receptor and is distinct from their affinity for intracellular cAMP-dependent protein kinase. Dose-response curves with cAMP and adenosine 3',5'-monophosphorothioate, a nonhydrolyzable analog, revealed that the requirement for high concentrations of exogenous cAMP for regulating gene expression is due to the rapid degradation of cAMP by phosphodiesterase. The addition of low concentrations of cAMP (100 nM) or analogs in pulses also regulates gene expression. Both the genes that are positively regulated by exogenous cAMP and the discoidin gene, which is negatively regulated, respond to cAMP analogs to the same degree. Genes expressed in prespore or prestalk cells are also similarly regulated. These data suggest that the effects are mediated through the same receptor. The specificity of this receptor is indistinguishable from that of the well-characterized cell surface cAMP receptor.
Mol Cell Biol 1986 Jul
PMID:Pharmacological characterization of cyclic AMP receptors mediating gene regulation in Dictyostelium discoideum. 302 32

The ret transforming gene was activated by recombination between two unlinked segments of human DNA, most likely during transfection of NIH 3T3 cells. To further define this transforming gene, we isolated and sequenced ret cDNA clones. The nucleotide sequence indicates that the active ret transforming gene encodes a fusion protein with a carboxy-terminal domain which is 40 to 50% homologous to members of the tyrosine kinase gene family. This tyrosine kinase domain is preceded by a hydrophobic sequence characteristic of a transmembrane domain. Transcription of the ret tyrosine kinase sequence was detected in the SK-N-SH neuroblastoma, HL-60 promyelocytic leukemia, and THP-1 monocytic leukemia cell lines, but not in 25 other human tumor cell lines surveyed. The ret tyrosine kinase may thus represent a cell surface receptor which is expressed in a restricted range of human cells.
Mol Cell Biol 1987 Apr
PMID:ret transforming gene encodes a fusion protein homologous to tyrosine kinases. 303 15

The T-cell surface glycoprotein CD4 is thought to function as a receptor for class II major histocompatibility complex molecules. Human CD4 is also the lymphoid cell receptor for human immunodeficiency virus, the causative agent of acquired immune deficiency syndrome. The observed infection of the central nervous system in acquired immune deficiency syndrome patients raises the possibility that CD4 is also present in nerve tissue and that a cell surface receptor for class II major histocompatibility complex antigens could play a role in central nervous system function. This possibility is reinforced by the detection of unique CD4-related transcripts in mouse and human brain tissue. In this study, the structure of the mouse brain CD4 transcript was determined. It is identical to the last two-thirds of the CD4 message and is capable of encoding a 217-residue protein that would consist of a truncated, 154-residue, cell surface region, together with the complete CD4 transmembrane and cytoplasmic regions. It would not include an amino-terminal hydrophobic leader peptide.
Mol Cell Biol 1988 May
PMID:Mouse brain CD4 transcripts encode only the COOH-terminal half of the protein. 326 Mar 31

Identification of the receptor-destroying enzyme of influenza C virus as a specific neuraminate O-acetylesterase has suggested that 9-O-acetyl-N-acetylneuraminic acid is an essential component of the cell surface receptor of influenza C virus (Herrler, G., Rott, R., Klenk, H.-D., Muller, H.-P., Shukla, A. K., and Schauer, R. (1985) EMBO (Eur. Mol. Biol. Organ.) J. 4, 1503-1506). In this report, three common sialic acids, N-acetylneuraminic acid (NeuAc), N-glycollylneuraminic acid (NeuGc), and 9-O-acetyl-N-acetylneuraminic acid (9-O-Ac-NeuAc) were compared for their ability to mediate attachment of influenza A, B, and C viruses to cells. Human asialoerythrocytes were resialylated to contain the three sialic acids in defined sequence on glycoprotein carbohydrate groups using purified sialyltransferases and corresponding CMP-sialic acid donor substrates. While influenza C virus failed to agglutinate native cells or resialylated cells containing NeuAc and NeuGc, resialylated cells containing 9-O-Ac-NeuAc in three different sialyloligosaccharide sequences were agglutinated in high titer. In contrast, most representative influenza A and B viruses examined preferentially agglutinated cells containing NeuAc and NeuGc and failed to agglutinate cells containing 9-O-Ac-NeuAc. Cells containing 9-O-Ac-NeuAc were sensitive to the action of influenza C virus neuraminate O-acetylesterase which converts 9-O-Ac-NeuAc to NeuAc. This treatment abolished agglutination by influenza C while making the cells agglutinable by several influenza A and B viruses. Finally, the ability of influenza C virus to agglutinate the erythrocytes of various species correlated with the presence of 9-O-Ac-NeuAc. The results provide direct evidence that influenza C virus utilizes 9-O-acetyl-N-acetylneuraminic acid as the primary receptor determinant for attachment to cell surface receptors.
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PMID:Influenza C virus uses 9-O-acetyl-N-acetylneuraminic acid as a high affinity receptor determinant for attachment to cells. 370 Mar 79


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