Coordinately and differentially mutable activities of torpedo, the Drosophila melanogaster homolog of the vertebrate EGF receptor gene

1990 ◽  
Vol 6 ◽  
pp. 74 ◽  
Keyword(s):  
Drosophila Melanogaster ◽  
Egf Receptor ◽  
Receptor Gene

scholarly journals Targeted Expression of the Class II Phosphoinositide 3-Kinase in Drosophila melanogaster Reveals Lipid Kinase-Dependent Effects on Patterning and Interactions with Receptor Signaling Pathways

2004 ◽  
Vol 24 (2) ◽  
pp. 796-808 ◽  
Author(s):  
Lindsay K. MacDougall ◽  
Mary Elizabeth Gagou ◽  
Sally J. Leevers ◽  
Ernst Hafen ◽  
Michael D. Waterfield
Keyword(s):  
Drosophila Melanogaster ◽  
Signaling Pathways ◽  
Egf Receptor ◽  
Adaptor Protein ◽  
Class Ii ◽  
Notch Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Class I ◽  
Wing Venation ◽  
Receptor Signaling

ABSTRACT Phosphoinositide 3-kinases (PI3Ks) can be divided into three distinct classes (I, II, and III) on the basis of their domain structures and the lipid signals that they generate. Functions have been assigned to the class I and class III enzymes but have not been established for the class II PI3Ks. We have obtained the first evidence for a biological function for a class II PI3K by expressing this enzyme during Drosophila melanogaster development and by using deficiencies that remove the endogenous gene. Wild-type and catalytically inactive PI3K_68D transgenes have opposite effects on the number of sensory bristles and on wing venation phenotypes induced by modified epidermal growth factor (EGF) receptor signaling. These results indicate that the endogenous PI3K_68D may act antagonistically to the EGF receptor-stimulated Ras-mitogen-activated protein kinase pathway and downstream of, or parallel to, the Notch receptor. A class II polyproline motif in PI3K_68D can bind the Drk adaptor protein in vitro, primarily via the N-terminal SH3 domain of Drk. Drk may thus be important for the localization of PI3K_68D, allowing it to modify signaling pathways downstream of cell surface receptors. The phenotypes obtained are markedly distinct from those generated by expression of the Drosophila class I PI3K, which affects growth but not pattern formation.

Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease

1988 ◽  
Vol 8 (10) ◽  
pp. 4174-4184
Author(s):  
A C Johnson ◽  
Y Jinno ◽  
G T Merlino
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Receptor Gene ◽  
Gene Promoter ◽  
Direct Repeat ◽  
S1 Nuclease ◽  
Epidermal Growth ◽  
Specific Factors

The epidermal growth factor (EGF) receptor is the functional target of the mitogen EGF and the cellular homolog of the avian erythroblastosis virus erbB oncogene product. Regulation of expression of the proto-oncogene encoding the EGF receptor can be elucidated by studying the structure and function of the gene promoter outside the confines of the cell. Previously, we reported the isolation of the human EGF receptor gene promoter. The promoter is highly GC rich, contains no TATA or CAAT box, and has multiple transcription start sites. An S1 nuclease-sensitive site has now been found 80 to 110 base pairs (bp) upstream from the major in vivo transcription initiation site. Two sets of direct repeat sequences were found in this area; both conform to the motif TCCTCCTCC. When deletion mutations were made in this region of the promoter by using either Bal 31 exonuclease or S1 nuclease, we found that in vivo activity dropped three- to fivefold, on the basis of transient-transfection analysis. Examination of nuclear protein binding to normal and mutated promoter DNAs by gel retardation analysis and DNase I footprinting revealed that two specific factors bind to the direct repeat region but cannot bind to the S1 nuclease-mutated promoter. One of the specific factors is the transcription factor Sp1. The results suggest that these nuclear trans-acting factors interact with the S1 nuclease-sensitive region of the EGF receptor gene promoter and either directly or indirectly stimulate transcription.

scholarly journals Human tumor cell lines with EGF receptor gene amplification in the absence of aberrant sized mRNAs

1985 ◽  
Vol 13 (23) ◽  
pp. 8477-8486 ◽  
Author(s):  
C.Richter King ◽  
Matthias H. Kraus ◽  
Lewis T. Williams ◽  
Glenn T. Merlino ◽  
Ira H. Pastan ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Gene Amplification ◽  
Egf Receptor ◽  
Receptor Gene ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Decreased expression of hepatic epidermal growth factor receptor gene in diabetic mice

1989 ◽  
Vol 3 (1) ◽  
pp. 49-56 ◽  
Author(s):  
S. Kasayama ◽  
M. Yoshimura ◽  
T. Oka
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Messenger Rnas ◽  
Diabetic Mice ◽  
Structural Protein ◽  
Epidermal Growth ◽  
Genetically Diabetic Mice

ABSTRACT The expression of hepatic epidermal growth factor (EGF) receptor gene was studied in genetically diabetic (C57BL/KsJ db/db) mice and streptozotocininduced diabetic mice. The binding of 125I-labelled EGF to hepatic membrane preparations of genetically diabetic mice was only 35% of that of non-diabetic mice. Levels of EGF receptor messenger RNAs (10 and 6 kb) in the liver of the diabetic animals were also reduced by about 75%. In streptozotocin-induced diabetic mice, levels of hepatic EGF binding and messenger RNAs for EGF receptor were decreased to 27 and 30% of control levels respectively, at 5 weeks after injection of the drug. There were, however, no significant differences in levels of messenger RNAs for the structural protein β-actin in the liver. In addition, levels of EGF receptor messenger RNAs in the kidney were similar between control and the two kinds of diabetic mice. Daily administration of insulin to the streptozotocin-induced diabetic mice increased the hepatic levels of EGF receptor messenger RNAs to almost normal levels. These results indicate that EGF binding to its receptor decreases in the liver of diabetic mice, involving alterations in the level of EGF receptor messenger RNAs, and that insulin is important for the regulation of EGF receptor gene expression in the liver but not in the kidney.

scholarly journals Expression and biosynthetic variation of the epidermal growth factor receptor in human hepatocellular carcinoma-derived cell lines.

1988 ◽  
Vol 8 (1) ◽  
pp. 25-34 ◽  
Author(s):  
C R Carlin ◽  
D Simon ◽  
J Mattison ◽  
B B Knowles
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Cell Lines ◽  
Gene Amplification ◽  
Egf Receptor ◽  
Hepatoma Cell ◽  
Receptor Gene ◽  
Epidermal Growth

Expression of the epidermal growth factor (EGF) was analyzed in six human hepatocellular carcinoma-derived and one human hepatoblastoma-derived cell line, each of which retained the differentiated phenotype and functions of the parenchymal hepatocyte. The level of receptor expression of each hepatoma cell line was similar to that of the normal human fibroblast, approximately 10(5) molecules per cell. However, NPLC/PRF/5, a subline of the PLC/PRF/5 cell line obtained following reestablishment of a xenograft tumor in vitro, was found to express 4 x 10(6) high-affinity EGF receptor molecules per cell. Proliferation of the NPLC/PRF/5 cell line was inhibited in the presence of nanomolar quantities of ligand. Receptor overexpression was found to result from EGF receptor gene amplification without apparent rearrangement of the EGF receptor coding sequences. Although cell-specific variability in posttranslational processing of EGF receptor N-linked oligosaccharides in the hepatoma cell lines was found, no difference between the receptors in PLC/PRF/5 and NPLC/PRF/5 was observed and no aberrant receptor-related species were detected. EGF receptor gene amplification in the NPLC/PRF/5 cell line is probably a reflection of genome instability and selection of variants with augmented growth potential in limiting concentrations of EGF in vivo. When viewed in this light, EGF receptor overexpression could represent a manifestation of tumor progression in the EGF-responsive hepatocyte.

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