Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha2-Heremans Schmid glycoprotein (alpha2-HSG) is a member of the fetuin family of serum proteins whose biological functions are not completely understood. There is a consensus that alpha2-HSG plays a role in the regulation of tissue mineralization. However, one aspect of alpha2-HSG function that remains controversial is its ability to inhibit the insulin receptor tyrosine kinase and the biological actions of insulin. Interestingly, some studies suggest that alpha2-HSG differentially inhibits mitogenic, but not metabolic, actions of insulin. However, these previous studies were not carried out in bona fide insulin target cells. Therefore, in the present study we investigate the effects of alpha2-HSG in the physiologically relevant rat adipose cell. We studied insulin-stimulated translocation of the insulin-responsive glucose transporter GLUT4 in transfected rat adipose cells overexpressing human alpha2-HSG. In addition, we measured insulin-stimulated glucose transport in adipose cells cultured with conditioned medium from the transfected cells as well as in freshly isolated adipose cells treated with purified human alpha2-HSG. Compared with control cells, we were unable to demonstrate any significant effect of alpha2-HSG on insulin-stimulated translocation of GLUT4 or glucose transport. In contrast, we did demonstrate that overexpression of alpha2-HSG in adipose cells inhibits both basal and insulin-stimulated phosphorylation of Elk-1 (a transcription factor phosphorylated and activated by mitogen-activated protein kinase and other related upstream kinases). Interestingly, we did not observe any major effects of alpha2-HSG to inhibit insulin-stimulated phosphorylation of the insulin receptor, insulin receptor substrate-1, -2, or -3, in either transfected or freshly isolated adipose cells. We conclude that alpha2-HSG inhibits insulin-stimulated Elk-1 phosphorylation, but not glucose transport, in adipose cells by a mechanism that may involve effector molecules downstream of insulin receptor substrate proteins.
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PMID:Alpha2-Heremans Schmid glycoprotein inhibits insulin-stimulated Elk-1 phosphorylation, but not glucose transport, in rat adipose cells. 975 94

CD44 has diverse functions in cell-cell and cell-matrix interactions and may be a determinant of metastatic and invasive behaviour in carcinomas. The immunohistochemical expression of CD44 in a series of 110 colorectal carcinomas and 25 adenomas was examined using the monoclonal mouse anti-human phagocytic glycoprotein-1, CD44 (clone DF 1485) in correlation with the expression of basement membrane (BM) antigens (type IV collagen, laminin), fibronectin, cathepsin D, p53, Rb, bcl-2, c-erbB-2, EGFR, proliferation indices (Ki-67, PCNA) and with other conventional clinicopathological variables. In adenomas, low CD44 expression (<10% of neoplastic cells) was present in 16%, moderate (10-50% of neoplastic cells) in 52% and extensive (>50% of neoplastic cells) in 32% of cases. In carcinomas, low CD44 expression was found in 14.5%, moderate in 28.2% and extensive in 57.30%. Although the CD44 expression was higher in carcinomas than in adenomas, we found no statistically significant difference between these two groups. CD44 expression in carcinomas was positively correlated with tumour size (P=0.018), tumour cells cathepsin D (P=0.022), stromal cell cathepsin D (P=0.003) and Rb protein (P=0.021). An inverse correlation was observed between CD44 and the anti-apoptotic protein expression bcl-2 in adenocarcinomas (P=0.039) and in adenomas (P=0.021). These data suggest that CD44 may be involved in the process of invasion and metastasis, probably with the cooperation of cathepsin D. Its expression may be an indicator of poor prognosis in colorectal adenocarcinomas.
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PMID:Glycoprotein CD44 expression in colorectal neoplasms. An immuno-histochemical study including correlation with cathepsin D, extracellular matrix components, p53, Rb, bcl-2, c-erbB-2, EGFR and proliferation indices. 1007 Dec 34

To investigate the nature and intracellular behavior of the matrix (M) protein of an avirulent strain (HEP-Flury) of rabies virus, we cloned and sequenced the cDNA of the protein. Using expression vectors pZIP-NeoSV(X)1 and pCDM8, the cDNA was transfected to animal cells (BHK-21 and COS-7) with or without coexpression of viral glycoprotein (G). When M protein alone was expressed in the cells, it displayed homogeneous distribution in the whole cell including the nucleus. In contrast, coexpression with G protein resulted in the abolishment of nuclear distribution of M antigen, and both of the antigens displayed a colocalized distribution in the cell, especially at the cellular membrane as seen in the virus-infected cells, while the distribution of G antigen was not affected by coexpressed M antigen. Immunoprecipitation studies revealed that M protein was coprecipitated with G protein by anti-G antibody, and vice versa, although cross-linking with dithiobis(succinimidyl propionate) was necessary for coprecipitation because of their easier dissociation in the presence of sodium deoxycholate. These results suggest that M protein intimately associates with G protein, which may affect or regulate the behavior (e.g., intracellular localization) of M protein. Studies with deletion mutants of M protein indicate that an internal region around the amino acids from 115 to 151 is essential for the M protein to preserve its binding ability to G protein.
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PMID:Intracellular behavior of rabies virus matrix protein (M) is determined by the viral glycoprotein (G). 1033 96

A lectin was isolated from the mycelium of the stationary growing enthomopathogenic fungus Beauveria bassiana by extraction, chromatography on QAE-Sephadex A-25, salt precipitation, and hydrophobic chromatography on Phenyl-Sepharose 4B. The Beauveria bassiana lectin (BBL) is a 15 kDa glycoprotein rich in hydrophobic amino acids, without detectable amount of methionine. It contains 12.6% of carbohydrates including galactose and mannose. Isoelectric point was found at pH 7.1. The lectin is stable between pH 6 and 11, and at temperature under 50 degrees C. The activity of the lectin was not dependent on with Ca++, Mn++, Mg++ cations and was apparently not blood group ABO specific. The hemagglutination caused by the lectin was inhibited by alpha lactose (Gal beta 1-->4 Glc alpha), but not by beta lactose (Gal beta 1-->4 Glc beta). In direct ELISA the BBL preferentially reacted with some glycoproteins carrying O-linked sugar structure Gal beta 1-->3 GalNAc: strongly with human glycophorin A and weaker with mouse glycophorin, fetuin, IgA, ovine submaxillary mucin. On the other hand BBL did not react in direct ELISA with N-glycoproteins (alpha 1-acid glycoprotein, haptoglobin, fibronectin), however, N-glycoproteins could act as inhibitors of lectin-glycophorin A interaction. We observed also weak interaction with asialo-Tamm-Horsfall N-glycoprotein having unusual large, branched N-glycans with outer GalNAc beta 1-->4Gal sequence. Moreover, the interaction of BBL with highly sialylated preparations of glycoproteins was weaker than with asialo forms. Presented results indicate that BBL exhibits sugar binding specificity towards glycotope corresponding to Thomsen-Friedenreich antigen and its related sequences: Gal beta 1-->3 GalNAc > Neu Ac alpha 2-3 Gal beta 1-->3 (Neu Ac alpha 2-6) GalNAc > Gal beta 1-->4 Glc alpha.
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PMID:Lectin from Beauveria bassiana mycelium recognizes Thomsen-Friedenreich antigen and related structures. 1042 10

Previous results have indicated that incorporation of surface glycoprotein into retroviral particles is not a specific process and that many heterologous viral and cellular glycoproteins can be incorporated as long as they do not have long cytoplasmic C-terminal regions which were presumed to be sterically inhibitory. In this study, this concept has been directly examined by analyzing the incorporation of the wild-type human epidermal growth factor receptor (Wt-EGFR) and of a C-terminally truncated mutant of Wt-EGFR (Tr-EGFR) into human immunodeficiency virus (HIV)-like particles. Incorporation was directly analyzed at the protein level and by immunogold labelling of enriched HIV-like particles. In agreement with the above concept, Tr-EGFR, with only 7 C-terminal amino acids (aa), was efficiently incorporated into HIV-like particles. Incorporation of the Wt-EGFR species, with 542 C-terminal cytoplasmic aa, was reduced by a factor of about 5 in comparison to that of the Tr-EGFR species. However, the Wt-EGFR species was still very significantly present in the HIV-like particles. A series of control experiments verified that this represents genuine incorporation of Wt-EGFR into the membrane of HIV-like particles. These observations allow further speculation as to the processes governing glycoprotein incorporation into retroviral particles and indicate that the internal virus structure of HIV (in particular the matrix layer [MA]) can accommodate much larger heterologous cytoplasmic domains in incorporated glycoproteins than previously assumed.
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PMID:Incorporation of wild-type and C-terminally truncated human epidermal growth factor receptor into human immunodeficiency virus-like particles: insight into the processes governing glycoprotein incorporation into retroviral particles. 1051 38

The in vitro radiation sensitivity of CFU-Meg isolated from human placental and umbilical cord blood was evaluated in plasma clot cultures stimulated by recombinant human cytokines, including thrombopoietin, the FLT3 ligand (FLT3LG), interleukin-3, interleukin-11 and stem cell factor. The CD34(+) cells were irradiated with X rays at a dose rate of 73 cGy/ min. The megakaryocyte colonies were identified by using an FITC-conjugated antibody to glycoprotein IIbIIIa and were classified into two groups based on colony size: large colonies (immature CFU-Meg) and small colonies (mature CFU-Meg). Treatment with thrombopoietin alone or in combination with FLT3LG and/or interleukin-11 gave exponential radiation survival curves (D(0) for immature CFU-Meg = 56-77 cGy, D(0) for mature CFU-Meg = 86 cGy-1.12 Gy), while marked shoulders were observed on the survival curves for colonies supported by the combination of thrombopoietin, interleukin-3 and stem cell factor (D(0) for immature CFU-Meg = 89- 98 cGy; D(0) for mature CFU-Meg = 1. 25-1.31 Gy). Our results showed that the immature CFU-Meg were more radiosensitive than the mature CFU-Meg and that the combination of cytokines, including thrombopoietin, interleukin-3 and stem cell factor, affected the radiation sensitivity of CFU-Meg to the same extent as with thrombopoietin alone or in combination with FLT3LG and/or interleukin-11.
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PMID:Radiation sensitivity of megakaryocyte colony-forming cells in human placental and umbilical cord blood. 1062 13

Hepatocyte growth factor (HGF) identical to scatter factor (SF) is a glycoprotein involved in the development of a number of cellular phenotypes, including proliferation, mitogenesis, formation of branching tubules and, in the case of tumour cells, invasion and metastasis. This fascinating cytokine transduces its activities via its receptor encoded by the c-met oncogene, coupled to a number of transducers integrating the HGF/SF signal to the cytosol and the nucleus. The downstream transducers coupled to HGF/MET, most of which participate in overlapping pathways, determine the development of the cell's phenotype, which in most cell types is dual.
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PMID:Hepatocyte growth factor/scatter factor-induced intracellular signalling. 1071 61

In mammalian cells, the binding of epidermal growth factor (EGF) to its receptor (EGFR), a glycoprotein with intrinsic tyrosine kinase activity, leads to the pleiotropic responses to EGF. Among these, a negative feedback response by stimulation of receptor internalization and lysosomal degradation, this attenuating signal transduction. In this work, data are reported on the identification of specific EGFRs in isolated digestive gland cells from the marine mussel (Mytilus galloprovincialis Lam.) By immunoelectron microscopy. In control digestive cells, EGFR immunoreactivity was mainly associated with cytoplasmic membrane structures and, to a lesser extent, the cell membrane. The presence of EGFR-like receptors was confirmed by Western blotting of digestive gland cell extracts with two different monoclonal antibodies that recognize either intracellular or extracellular epitopes. The addition of mammalian EGF resulted in significant time and temperature-dependent changes in EGFR subcellular distribution in mussel cells. In cells exposed to EGF for 0-15 min at 4 degrees C, the distribution of EGFR was not significantly different from that of the control cells. On the other hand, at 18 degrees C, an increased labelling along the cell membrane was observed after 5-10 min after EGF addition, with a concomitant decrease in the cytoplasmic signal. Moreover, after 20 min of exposure to EGF, ligand binding apparently resulted in EGFR compartmentation within the lysosomes. These observations were confirmed by quantitative analysis of EGFR labelling at different times of EGF exposure. Similar results were obtained utilizing the two different monoclonal antibodies. The results indicate that, in mussel digestive cells, the binding of heterologous EGF to specific receptors induces a negative feedback response by stimulating the lysosomal degradation of EGFR, thus suggesting the presence of mechanisms responsible for receptor downregulation similar to those observed in mammalian cells.
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PMID:Immunoelectron microscope analysis of epidermal growth factor receptor (EGFR) in isolated Mytilus galloprovincialis (Lam.) digestive gland cells: evidence for ligand-induced changes in EGFR intracellular distribution. 1079 21

Chinese hamster ovary (CHO) cell mutants defective in the disintegration of endocytosed low-density lipoprotein (LDL) were isolated from mutagenized cells by repeated flow-cytometric cell sorting. After seven rounds of cell sorting, we obtained mutant pools, from which nine mutant clones were established. These mutant strains were all recessive, and were categorized into three complementation groups A, B, and C. The previously established CHO mutant, LEX1 (Lysosome-Endosome X1), fell into the complementation group A. One of the newly isolated mutants, LEX2, fell into the complementation group B, and showed slower degradation of RET-LDL than LEX1 cells. LEX2 showed prominence of well-elaborated multivesicular bodies (MVBs), positive for lysosomal glycoprotein-B/cathepsin D and cation-independent mannose 6-phosphate receptor (CI-MPR), yet negative for transferrin receptor or rab7. Endocytosed intact LDL accumulated in these CI-MPR-positive structures starting at 10-15 minutes of internalization and the accumulation reached completion at 20 minutes. Intermixing of separately internalized fluorescent LDLs between the LEX2 MVBs was slow and saturable at a lower level than observed between late endosomes/lysosomes in wild-type or in LEX1 cells. The receptor recycling pathway to the plasma membrane and the acidification of intracellular compartments were normal in LEX2 cells. These results are consistent with the idea that LEX2 cells are defective in the segregation and sequestration of contents at compartments equivalent to the transport intermediates, previously referred to as endosomal carrier vesicles or maturing MVBs. This MVB stage is likely to be an earlier stage than rab7-positive, lysosome-interacting late endosomes observed in LEX1 cells. Thus, LEX1 and LEX2 mutations could be considered as landmarks for these distinct late endocytic stages, and use of these cells in biochemical and molecular genetic analyses would help to understand the as yet unidentified details of late endocytic pathways including the MVB dynamics.
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PMID:Arrested maturing multivesicular endosomes observed in a Chinese hamster ovary cell mutant, LEX2, isolated by repeated flow-cytometric cell sorting. 1082 92

This study reports the first use of gene array technology for the identification of a tumor-specific marker in lymphoid neoplasms. The differential gene expression of 31 hematopoietic cell lines, representing most major lymphoma subgroups of B- and T-cell origin, was assessed by hybridizing labeled complementary DNA to Atlas human expression arrays containing 588 genes. Genes known to be specific for B, T, or myelomonocytic lineages were appropriately identified in the arrays, validating the general utility of this approach. One gene, clusterin, not previously known to be expressed in lymphoid neoplasms, was specifically found in all 4 anaplastic large-cell lymphoma (ALCL) cell lines, but not in any of the 27 remaining tumor lines. Using a monoclonal antibody against clusterin, its differential expression was confirmed by Western blotting and immunohistochemistry. A total of 198 primary lymphomas (representing most major lymphoma subtypes), including 36 cases of systemic ALCL, were surveyed for clusterin expression by immunohistochemistry and Western blotting. All of the 36 ALCL cases marked for clusterin, with most cases showing moderate to strong staining in the majority of neoplastic cells. Clusterin expression was not related to expression of anaplastic lymphoma kinase-1. With 2 exceptions, none of the remaining 162 non-ALCL cases marked with the clusterin antibody, including Hodgkin disease and primary cutaneous ALCL. In reactive lymphoid tissues, only follicular dendritic cells and fibroblastic reticular cells exhibited staining. Clusterin is a highly conserved glycoprotein implicated in intercellular and cell matrix interactions, regulation of the complement system, lipid transport, stress responses, and apoptosis. Although its function in ALCL is unknown, the unique expression of clusterin within this category of lymphoma provides an additional marker for the diagnosis of ALCL. This study illustrates the enormous potential of gene array technologies for diagnostic marker discovery. (Blood. 2000;96:398-404)
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PMID:Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas. 1088 98


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