In vivo effects of epidermal growth factor on epidermal pattern formation and hair follicle initiation in the marsupial bandicoot Isoodon macrourus

1997 ◽  
Vol 9 (5) ◽  
pp. 493 ◽  
Author(s):  
David L. Adelson ◽  
David E. Hollis ◽  
James C. Merchant ◽  
Bronwyn A. Kelley
Keyword(s):  
Growth Factor ◽  
Pattern Formation ◽  
Epidermal Growth Factor ◽  
Hair Follicle ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Hair Follicles ◽  
Sweat Glands ◽  
Epidermal Growth

The extrauterine development of marsupial pouch young (northern brown bandicoot Isoodon macrourus) has facilitated the study of the effects of murine epidermal growth factor (mEGF) on pattern formation in skin. Hair follicle initiation and development, which in the mouse would occur from about Days 13–14 of gestation onward, occurs postnatally. In the present study the effect in vivo of mEGF on developing skin corresponding to mouse gestational ages from Day 13 onward was examined. Subcutaneous injections of mEGF (0· 5, 1 ·0 and 2· 0 µg g-1 body weight) or equivalent volumes of saline (0· 9% w/w) were administered daily, before and during hair follicle initiation and development. Murine EGF inhibited the formation of hair follicles, hair follicle sweat glands, sebaceous glands and dermal papillae. The pattern of follicle initiation was perturbed. The characteristic trio follicle grouping was absent, and follicle rudiment densities (no. per mm2skin surface) were significantly lower in animals treated with mEGF, whereas follicle diameters were increased. These data may reflect a role for the epidermal growth factor (EGF) receptor in epidermal pattern formation. The EGF receptor and its potential ligands (such as EGF, transforming growth factor (TGF-α) or other yet-to-be-discovered ligands) perhaps act as parts of a pattern-forming system in vertebrate skin. Extra keyword: EGF receptor.

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 Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal growth factor receptors in blastlike cells of myelomonocytic origin

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2385-2392 ◽  
Author(s):  
TM Walz ◽  
C Malm ◽  
BK Nishikawa ◽  
A Wasteson
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Precursor Cells ◽  
Transforming Growth Factor Alpha ◽  
Epidermal Growth ◽  
Factor Alpha

The expression of transforming growth factor-alpha (TGF-alpha) in human differentiating leukemic cell lines and in circulating human eosinophils prompted the search for an analogous function in normal human bone marrow (BM) cells. Immunohistochemistry, using a monoclonal antibody directed to the mature form of the TGF-alpha molecule, showed TGF-alpha on the erythroblasts of normal donors. This novel property of erythroid cells was found on cells at all stages of maturation, most clearly on nucleated forms but to some extent also on erythrocytes within the BM. The presence of membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF-alpha antibodies; the recovered cells consisted almost entirely of erythroblasts. Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry showed a different pattern of positive cells including eosinophilic precursor cells, in accordance with earlier findings in blood eosinophils. In addition, the TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in BM cells was demonstrated by reverse transcription polymerase chain reaction, whereas EGF receptor-carrying cells were recognized by immunohistochemistry, using polyclonal antibodies directed to the cytoplasmic part of the EGF receptor. The EGF receptor-positive cell constituted about 3% of the nucleated BM cell population. It was classified as a blastlike cell of myelomonocytic origin by morphologic criteria and CD68 positivity. Our results may indicate a novel function of TGF-alpha in erythrocytic differentiation.

scholarly journals Five enzymes of the glycolytic pathway serve as substrates for purified epidermal-growth-factor-receptor kinase

1986 ◽  
Vol 239 (3) ◽  
pp. 691-697 ◽  
Author(s):  
N Reiss ◽  
H Kanety ◽  
J Schlessinger
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Glycolytic Pathway ◽  
Dependent Manner ◽  
Receptor Kinase ◽  
Epidermal Growth

Several enzymes of the glycolytic pathway are phosphorylated in vitro and in vivo by retroviral transforming protein kinases. These substrates include the enzymes phosphoglycerate mutase (PGM), enolase and lactate dehydrogenase (LDH). Here we show that purified EGF (epidermal growth factor)-receptor kinase phosphorylates the enzymes PGM and enolase and also the key regulatory enzymes of the glycolytic pathway, phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in an EGF-dependent manner. Stoichiometry of phosphate incorporation into GAPDH (calculated from native Mr) is the highest, reaching approximately 1. LDH and other enzymes of the glycolytic pathway are not phosphorylated by the purified EGF-receptor kinase. These enzymes are phosphorylated under native conditions, and the Km values of EGF-receptor kinase for their phosphorylation are close to the physiological concentrations of these enzymes in the cell. EGF stimulates the reaction by 2-5-fold by increasing the Vmax. without affecting the Km of this process. Phosphorylation is rapid at 22 degrees C and at higher temperatures. However, unlike the self-phosphorylation of EGF-receptor, which occurs at 4 degrees C, the glycolytic enzymes are poorly phosphorylated at this temperature. Some enzymes, in particular enolase, increase the receptor Km for ATP in the autophosphorylation process and thus may act as competitive inhibitors of EGF-receptor self-phosphorylation. On the basis of the Km values of EGF receptor for the substrate enzymes and for ATP in the phosphorylation reaction, these enzymes may also be substrates in vivo for the EGF-receptor kinase.

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