Cell surface receptors for endogenous mouse type C viral glycoproteins and epidermal growth factor: Tissue distribution in vivo and possible participation in specific cell-cell interaction

1980 ◽  
Vol 14 (3) ◽  
pp. 343-352 ◽  
Author(s):  
U. R. Rapp ◽  
Thomas H. Marshall
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Cell Interaction ◽  
Specific Cell ◽  
Surface Receptors ◽  
Viral Glycoproteins ◽  
Epidermal Growth ◽  
Type C

Kinetic analysis of the downregulation of epidermal growth factor receptors in rats in vivo

1990 ◽  
Vol 258 (4) ◽  
pp. C593-C598 ◽  
Author(s):  
S. Yanai ◽  
Y. Sugiyama ◽  
T. Iga ◽  
T. Fuwa ◽  
M. Hanano
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Kinetic Analysis ◽  
Intravenous Administration ◽  
Recovery Rate ◽  
Specific Binding ◽  
Control Level ◽  
Epidermal Growth

We previously clarified the specific binding sites for epidermal growth factor (EGF) in several organs in rats based on in vivo kinetic analysis (D. C. Kim, Y. Sugiyama, H. Sato, T. Fuwa, T. Iga, and M. Hanano. J. Pharm. Sci. 77: 200-207, 1988). In the present study, we have determined the extent of the receptor downregulation and the recovery rate of the available receptors for EGF in several organs in vivo. At the specified times (30 min-24 h) after intravenous administration of excess unlabeled EGF (300 micrograms/kg), the early-phase (less than 3 min) uptake clearances (k1) of the tracer amount of 125I-EGF, which are proportional to the cell-surface available receptor densities, were determined in the liver, kidney, duodenum, jejunum, ileum, stomach, and spleen. As the result, the k1 value in each organ at 30 min after intravenous administration of unlabeled EGF was lowered close to the receptor-independent clearance value, indicating that the cell-surface receptors were almost completely downregulated, and thereafter, the k1 value showed gradual recovery to the control level. Furthermore, the recovery half-lives showed interorgan differences, namely the half-life (20 min) in the liver was much shorter than those (2-4.5 h) in other organs. These results were considered to reflect the processes of the recycling of internalized EGF receptors to the cell-surface or recruitment of new receptors. It was concluded that the recovery rate of the downregulated receptors in the liver, which is most responsible for the plasma clearance of EGF, is much faster than those in other organs.

scholarly journals The Na+/H+ Exchanger Regulatory Factor Stabilizes Epidermal Growth Factor Receptors at the Cell Surface

2004 ◽  
Vol 15 (12) ◽  
pp. 5470-5480 ◽  
Author(s):  
Cheri S. Lazar ◽  
Catherine M. Cresson ◽  
Douglas A. Lauffenburger ◽  
Gordon N. Gill
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Growth Factor Receptors ◽  
Cell Surface Receptors ◽  
Epidermal Growth Factor Receptors ◽  
Regulatory Factor ◽  
Down Regulation ◽  
Surface Receptors ◽  
Epidermal Growth

Ligand binding to cell surface receptors initiates both signal transduction and endocytosis. Although signaling may continue within the endocytic compartment, down-regulation is the major mechanism that controls the concentration of cell surface receptors, their ability to receive environmental signals, and the ultimate strength of biological signaling. Internalization, recycling, and trafficking of receptor tyrosine kinases (RTKs) within the endosome compartment are each regulated to control the overall process of down-regulation. We have identified the Na+/H+ exchanger regulatory factor (NHERF) as an important molecular component that stabilizes epidermal growth factor receptors (EGFRs) at the cell surface to restrict receptor down-regulation. The NH2-terminal PDZ domain (PDZ 1) of NHERF specifically binds to an internal peptide motif located within the COOH-terminal regulatory domain of EGFR. Expression of NHERF slows the rate of EGF-induced receptor degradation. A point mutation that abolishes the PDZ 1 recognition sequence of EGFR enhances the rate of ligand-induced endocytosis and down-regulation of EGFR. Similarly, expression of a dominant negative mutant of NHERF enhances EGF-induced receptor down-regulation. In contrast to β-adrenergic receptors where NHERF enhances recycling of internalized receptors, NHERF stabilizes EGFR at the cell surface and slows the rate of endocytosis without affecting recycling. Although the mechanisms differ, for both RTKs and G protein-coupled receptors, the overall effect of NHERF is to enhance the fraction of receptors present at the cell surface.

Developing Concepts in Receptor Research

1983 ◽  
Vol 17 (5) ◽  
pp. 357-366 ◽  
Author(s):  
Pedro Cuatrecasas
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Cell Biology ◽  
Protein Chemistry ◽  
Coated Pits ◽  
Surface Receptors ◽  
Epidermal Growth ◽  
Receptor Research ◽  
Receptor Assays

Recent advances in molecular biology and protein chemistry have permitted spectacular progress in understanding the chemistry and cell biology of cell surface receptors for hormones and drugs. Methodological approaches, such as the use of radiolabeled ligands and direct receptor assays, have permitted the characterization, categorization, and purification of many receptors. The knowledge gained in understanding fundamental hormone-receptor interactions can form the basis of future, rational new drug design. Another important advance relates to the dynamic nature of receptors in their membrane environment. Upon binding of hormones such as insulin and epidermal growth factor, the complexes rearrange topographically on the cell surface, forming microclusters that are internalized into “receptosomes” via receptor-mediated endocytosis (which utilizes coated pits). The internalized receptor-hormone complex can have various fates, including the generation of selective signals for controlling cell growth and differentiation. In at least one case (epidermal growth factor), the latter may be dependent on the processes that occur in an acidic endosomal compartment within the cell.

Thrombin and epidermal growth factor become linked to cell surface receptors during mitogenic stimulation

Nature ◽  
1979 ◽  
Vol 278 (5706) ◽  
pp. 743-745 ◽  
Author(s):  
JOFFRE B. BAKER ◽  
ROBERT L. SIMMER ◽  
KEVIN C. GLENN ◽  
DENNIS D. CUNNINGHAM
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Cell Surface Receptors ◽  
Mitogenic Stimulation ◽  
Surface Receptors ◽  
Epidermal Growth
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