scholarly journals A nonmitogenic analogue of epidermal growth factor induces early responses mediated by epidermal growth factor.

1982 ◽  
Vol 92 (3) ◽  
pp. 687-693 ◽  
Author(s):  
Y Yarden ◽  
A B Schreiber ◽  
J Schlessinger
Keyword(s):  
Growth Factor ◽  
Membrane Proteins ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Ornithine Decarboxylase ◽  
Cell Morphology ◽  
Human Fibroblasts ◽  
Egf Receptors ◽  
Epidermal Growth ◽  
Stimulation Of

Cyanogen bromide-cleaved epidermal growth factor (CNBr-EGF) binds to EGF receptors with reduced affinity compared to the native hormone but fails to induce DNA synthesis. However, at similar receptor occupancy, CNBr-EGF is as potent as EGF in activating early cell responses to the hormone. The phosphorylation of membrane proteins, the stimulation of Na+-K+-ATPase as reflected by the ouabain-sensitive uptake of 86Rb of fibroblasts, changes in the organization of microfilaments and in cell-morphology, and the activation of the enzyme ornithine-decarboxylase are all induced by CNBr-EGF as well as EGF Our results are consistent with the notion that EGF-induced phosphorylation could act as a "second messenger" for the action of various EGF-induced responses such as activation of Na+-K+-ATPase, changes in the cytoskeleton and cell morphology, and the activation of the enzyme ornithine decarboxylase. However, the stimulation of phosphorylation of membrane proteins and other early responses are either not required or necessary but insufficient for the induction of DNA synthesis. Suboptimal concentrations of EGF together with CNBr-EGF stimulate DNA synthesis in human fibroblasts. Other growth factors such as insulin, fibroblast growth factor, and prostaglandin F2 alpha, which potentiate the mitogenic response of EGF, do not effect the response to CNBr-EGF. This suggests that the restoration of the mitogenic properties of CNBr-EGF by suboptimal doses of EGF occurs at the level of EGF receptors or during their processing.

scholarly journals An overexpressed gene transcript in senescent and quiescent human fibroblasts encoding a novel protein in the epidermal growth factor-like repeat family stimulates DNA synthesis.

1995 ◽  
Vol 15 (1) ◽  
pp. 120-128 ◽  
Author(s):  
B Lecka-Czernik ◽  
C K Lumpkin ◽  
S Goldstein
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Cellular Proliferation ◽  
Werner Syndrome ◽  
Human Fibroblasts ◽  
Extracellular Proteins ◽  
Gene Transcript ◽  
Epidermal Growth ◽  
Novel Protein

We carried out subtractive enrichment of a cDNA library derived from mRNA of senescent human diploid fibroblasts (HDF) established from a subject with Werner syndrome of premature aging. By differential screening, we isolated an overexpressed cDNA sequence (S1-5) that codes for a novel protein containing epidermal growth factor (EGF)-like domains which match the EGF-like consensus sequences within several known extracellular proteins that play a role in cell growth, development, and cell signalling. S1-5 mRNA is overexpressed in Werner syndrome and senescent normal HDF, is induced by growth arrest of young normal cells, but is significantly decreased by high serum, conditions which promote cellular proliferation. Paradoxically, microinjection into young HDF of two different lengths of S1-5 mRNA, containing different putative AUG translational start sites, consistently stimulated rather than inhibited DNA synthesis by an apparent autocrine/paracrine mechanism. Thus, the S1-5 gene product may represent a negative and/or positive factor whose ultimate activity is modulated by the cell environment as occurs with other members of EGF-like family.

Synergistic stimulation of Swiss mouse 3T3 fibroblasts by epidermal growth factor and other factors in human mammary secretions

1987 ◽  
Vol 112 (1) ◽  
pp. 151-159 ◽  
Author(s):  
A. N. Corps ◽  
D. M. Blakeley ◽  
J. Carr ◽  
L. H. Rees ◽  
K. D. Brown
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Protein Concentration ◽  
Gel Filtration ◽  
Functional Class ◽  
Swiss Mouse ◽  
Egf Receptors ◽  
3T3 Fibroblasts ◽  
Epidermal Growth ◽  
Stimulation Of

ABSTRACT The concentration of epidermal growth factor (EGF) in human mammary secretions was about 50 nmol/l for several weeks prepartum. It then fell to about 13 nmol/l within 4 days after parturition, in parallel with the decrease in protein concentration which is associated with the onset of lactation. In contrast, the concentration of EGF in urine samples from the same donors remained constant throughout this period. All the immunoreactive EGF in mammary secretions competed at the EGF receptors on Swiss mouse 3T3 fibroblasts. The stimulation of these cells by samples of mammary secretions was, however, much greater than that induced by EGF alone, indicating the presence of other factors which synergize with EGF. Gel filtration of mammary secretions revealed two major peaks of mitogenic activity, corresponding to EGF and a factor of higher molecular weight. The latter could synergize with added EGF, insulin or bombesin, and thus falls into a different functional class from any of these factors. J. Endocr. (1987) 112, 151–159

scholarly journals Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+.

1984 ◽  
Vol 98 (3) ◽  
pp. 1082-1089 ◽  
Author(s):  
C P Burns ◽  
E Rozengurt
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Cellular Proliferation ◽  
Weak Acid ◽  
Mechanisms Of Action ◽  
Epidermal Growth ◽  
Reversible Time ◽  
Stimulation Of

Initiation of DNA synthesis in confluent quiescent 3T3 cell cultures stimulated by epidermal growth factor (EGF), vasopressin, and insulin was abolished by removing extracellular Na+. The inhibition was reversible, time- and Na+-concentration-dependent, and not due to an effect on binding or internalization of 125I-EGF. Stimulation by combinations of other growth factors with different mechanisms of action was also affected by decreasing extracellular Na+, but with different half-maximal Na+ concentrations. When choline was used as an osmotic substitute for Na+, the decrease in DNA synthesis was correlated with the decrease in intracellular K+. In contrast, when sucrose was used there was stimulation of the Na+-K+ pump and maintenance of intracellular K+ that resulted in a somewhat higher rate of DNA synthesis at lowered extracellular Na+ compared to choline. Mitogenesis induced by epidermal growth factor, vasopressin, and insulin led to cytoplasmic alkalinization as determined by an increase in uptake of the weak acid 5,5-dimethyloxazolidine-2,4-dione. Experimental decrease in extracellular Na+ blocked this cellular alkalinization. Therefore, under some conditions the supply of extracellular Na+ may limit cellular proliferation because of a reduction in the provision of Na+ to the Na+/H+ antiport and resultant failure of alkalinization. We conclude that Na+ flux and its effect on intracellular K and pH has a major role in the complex system that regulates proliferation.

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