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Modulation of the epidermal growth factor receptor by basic fibroblast growth factor
1Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Journal of Cellular Physiology
|February 1, 1993
Summary
Basic fibroblast growth factor (bFGF) rapidly reduces epidermal growth factor (EGF) binding and slowly inhibits EGF receptor autophosphorylation in fibroblasts. These effects on EGF binding and receptor activity can be uncoupled, indicating distinct cellular mechanisms.
Area of Science:
- Cell biology
- Molecular signaling
- Biochemistry
Background:
- Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) are key signaling molecules involved in cell growth and differentiation.
- EGF exerts its effects by binding to the EGF receptor (EGFR), initiating intracellular signaling cascades.
- Understanding the cross-talk between different growth factor signaling pathways is crucial for deciphering complex cellular processes.
Purpose of the Study:
- To investigate the effects of bFGF on EGF binding and EGFR autophosphorylation in Swiss 3T3 fibroblasts and PC12 cells.
- To elucidate the molecular mechanisms underlying the modulation of EGFR activity by bFGF.
- To determine if protein kinase C is involved in the bFGF-mediated inhibition of EGF signaling.
Main Methods:
- Treatment of Swiss 3T3 fibroblasts and PC12 cells with bFGF.
- Measurement of EGF binding to its receptor.
- Assessment of EGF receptor autophosphorylation.
- Investigation of the role of protein kinase C and cycloheximide in the observed effects.
Main Results:
- bFGF treatment caused a rapid decrease in EGF binding and a slower inhibition of EGFR autophosphorylation in Swiss 3T3 fibroblasts.
- The reduction in EGF binding involved the loss of high-affinity binding sites and a decrease in lower-affinity sites.
- bFGF stimulated EGFR phosphorylation, and this effect was sensitive to cycloheximide, suggesting a role for protein synthesis.
- In PC12 cells, bFGF reduced EGF binding but did not inhibit EGFR autophosphorylation, demonstrating that these events can be uncoupled.
Conclusions:
- bFGF differentially regulates EGF binding and EGFR autophosphorylation in a cell-type-specific manner.
- The inhibition of EGF binding by bFGF is independent of protein kinase C.
- EGFR autophosphorylation inhibition by bFGF is dependent on protein synthesis, while EGF binding reduction is not, suggesting distinct regulatory pathways.