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)

The hybrid GH cell strain, 928-9b, isolated from PRL+ (prolactin [PRL] producing) GH4Cl and PRL (PRL non-producing) F1BGH(1)2C1 cells, has specific TRH (thyroliberin) receptors, yet does not respond to this peptide hormone. Unlike the parent strain, GH4C1, TRH does not stimulate synthesis or release of PRL in the hybrid strain. In contrast, treatment of 928-9b cells with another peptide, EGF (epidermal growth factor), stimulates both release and synthesis of PRL. The number of EGF receptors in the hybrid strain (2.5 x 10(3)/cell) and the affinity of these receptors for ligand (2.2 nM) are comparable to that of the parent strain, GH4C1. The EGF dose response curve is also essentially the same for parent and hybrid cells for the enhancement of PRL production. A 3-8-fold enhancement of PRL production is observed and 1/2 maximal enhancement occurs at approximately 5 x 10(-11) M EGF for both strains. TRH does not have any potentiating effect on EGF-induced stimulation of PRL release or PRL synthesis in the hybrid strain. Although EGF and TRH have similar biological effects in responsive GH cells, binding of one hormone to its receptors does not modulate the binding of the heterologous hormone. These findings demonstrate that more than one effect of TRH is defective in 928-9b cells even though EGF responses are intact. This suggests that 1) TRH-stimulated PRL release and TRH-stimulated PRL production have a common intermediate step, and 2) TRH and EGF have a different mechanism of action in GH cells.
Mol Cell Biochem 1984 Aug
PMID:Defective thyroliberin-induced prolactin synthesis and release in a hybrid GH strain. 609 7

EGF-Rs are cell membrane glycoproteins of wide distribution. They have not yet been fully characterized or purified but are probably molecules of 170-190,000 mol. wt. in most cells. The growth factor EGF binds and will saturate cell surface receptors with a KA of about 5 X 10(9) M-1 although a receptor class with an affinity in excess of 10(10) M-1 has been detected in some cells. The number of receptors on a cell does not determine the level of its response. Some cell types have receptors which bind EGF, but with no mitogenic response. The ways in which receptor affinity and/or number is modulated are described. This and other evidence is reviewed in a search for a suitable model of a mechanism of action on the cell, which best fits the current data. There is ample evidence that EGF binds to the receptor; that ligand-receptor complexes cluster or aggregate; and then are internalized and degraded, but evidence for a direct connection between internalization and the subsequent mitogenic response is lacking. Good correlations between internalization and mitogenic responses have been observed and developed into a theory of endocytic activation, but there is a body of evidence which cannot be accommodated by this theory. Instead, an alternative model is suggested.
Mol Cell Biochem 1981 Feb 11
PMID:Epidermal growth factor receptors. 626 Nov 14

PDGF is a potent mitogen that initiates the proliferation of quiescent fibroblastic cells. EGF and somatomedin C (or insulin) can replace the requirement for plasma to function synergistically with PDGF to stimulate DNA synthesis. PDGF, EGF and somatomedin C control discrete cellular events in the cell cycle. Cyclic AMP can potentiate the effects of polypeptide mitogens. The down-regulation of EGF receptors by PDGF and cyclic AMP brings about a loss of the requirement for exogenous EGF. The transient treatment of density-arrested fibroblasts with PDGF allows better study of synergistic actions of PDGF and plasma-derived factors. These synergistic interactions are important to understand in determining how multiple growth factors regulate cellular proliferation.
Mol Cell Endocrinol 1983 Aug
PMID:A model of cell cycle control: sequential events regulated by growth factors. 631 47

When KB cells are incubated for 1 h with human adenovirus type 2 or type 5 (1 microgram/ml) and a conjugate of epidermal growth factor and Pseudomonas exotoxin (EGF-PE), protein synthesis is inhibited by 80 to 90%. Under these conditions, neither adenovirus nor EGF-PE alone has any effect on host protein synthesis. Thus, adenovirus enhances the toxicity of EGF-PE. A number of antibodies to intact virus and capsid components were tested for their ability to block the enhancing activity and virus uptake. At appropriate dilutions, antibodies prepared against intact virus and penton base blocked the enhancing activity without affecting virus uptake. Antibodies against hexon and fiber blocked virus uptake and enhancing activity in parallel. These studies suggest that the penton base is important in lysis of the vesicles which contain adenovirus and EGF-PE, and this base allows virus and toxin to enter the cytoplasm.
Mol Cell Biol 1984 Aug
PMID:Evidence that the penton base of adenovirus is involved in potentiation of toxicity of Pseudomonas exotoxin conjugated to epidermal growth factor. 633 84

The effects of three putative growth factors and serum on [Me-3H]thymidine and Na125I incorporation into thyroid cell cultures have been examined. We found that serum and EGF could stimulate radioactively labelled thymidine incorporation into confluent cultures. However, both factors completely inhibited iodine uptake and organification at low concentrations. Insulin also stimulated [Me-3H]thymidine incorporation but had no adverse effect on thyroid differentiated function. TSH examined under the same conditions was not a growth factor but was essential to maintain differentiated functions. We conclude that thyroid growth and differentiation are not mutually exclusive processes. However, EGF and serum inhibit thyroid differentiated function at very low concentrations. Elucidation of the physiological role of these factors and their mechanism of action may lead to a greater understanding of thyroid hormone biosynthesis.
Mol Cell Endocrinol 1984 Dec
PMID:The effects of growth factors and serum on DNA synthesis and differentiation in thyroid cells in culture. 639 78

Porcine thyroid follicle cells, cultured in suspension, were employed to investigate the effects of immunoglobulin preparations from patients with colloid goitre, Graves' disease or Hashimoto's thyroiditis on thyroid growth in vitro. Epidermal growth factor (EGF, 19 ng/ml) was used as a reference for maximum growth stimulation and produced a 9-fold increase in [3H]thymidine incorporation. Immunoglobulins (1000 micrograms/ml) were found to increase [3H]thymidine incorporation compared to control: from 10 normal individuals 32 +/- 4% (mean +/- SEM, % of EGF response), from 10 patients with colloid goitre 26 +/- 4% (not significantly different from normal), from 10 patients with Graves' disease 19 +/- 3% (P less than 0.05) and from 15 patients with Hashimoto's thyroiditis 11 +/- 2% (P less than 0.001). No patient immunoglobulin preparation showed activity greater than that of normal individuals. The lower growth stimulatory activity in Graves' disease and Hashimoto's thyroiditis remained after heat inactivation of serum and is thought to reflect surface binding of thyroid autoantibodies.
Mol Cell Endocrinol 1984 Mar
PMID:Influence of thyroid autoantibodies on thyroid cellular growth in vitro. 660 95

Four antigenic variants of the 19-kDa carboxy terminal fragment of Plasmodium falciparum merozoite surface protein, MSP1 (MSP1(19)), were expressed in Saccharomyces cerevisiae as a histidine-tagged, secreted polypeptides (rMSP1(19)s). Structural analysis of the rMSP1(19)s indicated that a single amino acid change (E to Q) in the first EGF-like domain of the yeast-secreted rMSP1(19) proteins caused a significant change in their disulfide bond-dependent conformation. The antigenicity of the rMSP1(19)s were qualitatively and quantitatively analyzed by direct and competitive binding ELISAs. The data indicate that conserved and variant B cell determinants of MSP1(19), as well as epitopes that are known targets of protective antibodies, were recreated authentically in the rMSP1(19)s. Secretion of histidine-tagged rMSP1(19)s using the expression system described may be an efficient and effective means of producing a properly folded immunogen for a human vaccine against the blood stages of P. falciparum.
Mol Biochem Parasitol 1994 Feb
PMID:Expression and antigenicity of Plasmodium falciparum major merozoite surface protein (MSP1(19)) variants secreted from Saccharomyces cerevisiae. 751 93

To investigate the potential role of transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor (EGF-R) in the fibroproliferative response to acute lung injury, we determined lung steady-state TGF-alpha and EGF-R mRNA levels, TGF-alpha protein levels, and the distribution of TGF-alpha and EGF-R immunoreactive protein of bleomycin-injured and control rat lungs. At 2 and 4 days after a single intratracheal injection of bleomycin, TGF-alpha mRNA levels increased to 159% and 184% of control values, respectively. EGF-R mRNA levels increased to 163%, 314%, and 170% of control values at 1, 7, and 14 days after bleomycin instillation. TGF-alpha protein levels in whole lung extracts increased to 230% of control values at 4 days after bleomycin administration. TGF-alpha and EGF-R immunoreactivity was detected in macrophages, alveolar septal cells, and airway epithelium of control and bleomycin-injured animals with an apparent increase in the intensity and number of specifically immunostained cells following lung injury. TGF-alpha and EGF-R immunoreactive proteins were detected in foci of cellular proliferation and in areas of intraalveolar fibrosis. We conclude that TGF-alpha and the EGF-R are present in normal and bleomycin-injured rat lung and that the expression of this growth factor and its receptor are up-regulated following lung injury. These results suggest that increased expression of TGF-alpha and the EGF-R may be an important mechanism that modulates the fibroproliferative response to acute lung injury.
Am J Respir Cell Mol Biol 1994 Nov
PMID:Expression of transforming growth factor-alpha and epidermal growth factor receptor is increased following bleomycin-induced lung injury in rats. 752 66

Interferons (IFNs) exert antiproliferative effects on many types of cells. The underlying molecular mechanism, however, is unclear. One possibility is that IFNs block growth factor-induced mitogenic signaling, which involves activation of Ras/Raf-1/MEK/mitogen-activated protein kinase. We have tested this hypothesis by using HER14 cells (NIH 3T3 cell expressing both platelet-derived growth factor [PDGF] and epidermal growth factor [EGF] receptors) as a model system. Our studies showed that IFNs (alpha/beta and gamma) blocked PDGF-and phorbol ester- but not EGF-stimulated DNA synthesis and cell proliferation. While the ligand-stimulated receptor tyrosine phosphorylation and interaction with downstream signaling molecules, such as GRB2, were not affected, IFNs specifically blocked PDGF- and phorbol ester- but not EGF-stimulated activation of Raf-1, mitogen-activated protein kinases, and tyrosine phosphorylation of an unidentified 34-kDa protein. This inhibition could be detected as early as 5 min after IFN treatments and was insensitive to cycloheximide, indicating that de novo protein synthesis is not required. The IFN-induced inhibition acted upstream of Raf-1 kinase and downstream of diacyl glycerol/phorbol ester, suggesting that protein kinase C (PKC) is the potential primary target. Consistently, downregulation of PKC by chronic phorbol myristate acetate treatment or inhibition of PKC by H7 and staurosporine blocked PDGF- and phorbol myristate acetate- but not EGF-induced signaling and DNA synthesis. Moreover, incubating cells with antisense oligodeoxyribonucleotides of PKC delta eliminated production of PKC delta protein and specifically blocked PDGF- but not EGF-stimulated mitogenesis in these cells. Thus, these studies have elucidated a major difference in the early events of EGF-and PDGF-stimulated signal transduction and, more importantly, revealed a novel mechanism by which IFNs may execute their antiproliferative function.
Mol Cell Biol 1994 Dec
PMID:Interferons block protein kinase C-dependent but not-independent activation of Raf-1 and mitogen-activated protein kinases and mitogenesis in NIH 3T3 cells. 862 73

Growth factors differently regulate astroglial cell differentiation and proliferation. In an effort to understand the early intracellular events promoted by growth factors in astroglial cells, we have determined the effects of IGF1, insulin, PDGF, EGF and FGFs on phosphatidylinositol-3 kinase. IGF1, PDGF and EGF which stimulate cell proliferation of astroglial cells, increased phosphatidylinositol-3 kinase activity immunoprecipitated with anti-phosphotyrosine antibodies as shown by thin layer chromatography and high performance liquid chromatography. FGFa and FGFb, which strongly stimulate proliferation of astroglial cells, have no effect on phosphatidylinositol-3 kinase activity. Addition of 1 nM PDGF, 10 nM IGF1 or 100 nM EGF to the culture medium rapidly stimulated phosphatidylinositol-3 kinase activity which declined slowly after 2 min. The stimulation of phosphatidylinositol-3 kinase increased with growth factor concentration. The maximum increase in phosphatidylinositol-3 kinase activity occurred with 50 nM IGF1, 1 nM PDGF or 100 nM EGF. Since insulin was active only at high concentration (1 microM), its effect was probably mediated through IGF1 receptors and not through insulin receptors. Treatment with IGF1-plus-EGF, had an additive effect on PI(3)-kinase activity, PDGF-plus-IGF1 did not. IGF1 and PDGF, to a lesser degree, also increased the phosphatidylinositol-3 kinase activity associated with pp60c-src protein. Immunoblots performed with an antibody directed against the p85-subunit of the phosphatidylinositol-3 kinase confirmed that IGF1 increased the number of phosphatidylinositol-3 kinase molecules associated with phosphotyrosine-containing proteins or with c-src protein. Each growth factor affects in a different manner the association of phosphatidylinositol-3 kinase with phosphotyrosine-containing proteins and with c-src protein and thus probably modulates intracellular signals downstream of phosphatidylinositol-3 kinase in astroglial cells.
Cell Mol Biol (Noisy-le-grand) 1994 Jul
PMID:Growth factor-regulated phosphatidylinositol-3-kinase in astrocytes. Involvement of pp60c-src. 752 18


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