Basic fibroblast growth factor (FGF-2) is synthesized as different molecular mass isoforms all lacking the signal-peptide sequence. The high molecular-mass isoforms (21–24 kDa) possess a signal sequence directing their nuclear translocation. The role of each isoform is still poorly understood, however, modifications in intracellular signalling pathways could explain some effects of these peptides. In order to evaluate the role of FGF-2 isoforms on the adenylate cyclase (AC) signalling pathway, we retrovirally infected a rat pancreatic cell line (AR4-2J) with point-mutated FGF-2 cDNAs, allowing the expression of the 18 (A5 cells) or 22.5 kDa isoform (A3 cells) at a low level. In membrane preparations of A3 cells, unscheduled expression of the 22.5 kDa FGF-2 isoform induced a 2-fold decrease in both basal and forskolin-stimulated AC activity. Studies carried out on intact cells also showed decreased accumulation of cAMP in A3 cells in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Both FGF-2 peptides also induced functional modifications of G-proteins without affecting their levels. The 22.5 kDa peptide led to enhanced ADP-ribosylation of both αs-subunits in vitro, whereas the expression of the low molecular-mass 18 kDa peptide resulted in a 2-fold increase in αi2 and α0 ADP-ribosylations. Furthermore, control CAT cells (AR4-2J cells transfected with the retrovirus containing the chloramphenicol acetyltransferase gene) and A5 cells were growth-inhibited by 8-Br-cAMP, in contrast to A3 cells. These data provide evidence that the expression of FGF-2 peptides could play a role in cell functions by modifying the AC signalling pathway. FGF-2 peptides are able to modulate both AC activity and the regulatory G-proteins. Finally FGF-2 expression may interfere with cAMP-regulated cell proliferation.
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Research Article|
April 15 1996
Cells retrovirally transfected with fibroblast growth factor-2 isoforms exhibit altered adenylate cyclase activity and G-protein functionality
Agnes ESTIVAL;
Agnes ESTIVAL
*INSERM U. 151, CHU Rangueil, 31054 Toulouse cedex, France
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Patrick ROBBERECHT;
Patrick ROBBERECHT
*INSERM U. 151, CHU Rangueil, 31054 Toulouse cedex, France
†Laboratoire de Chimie Biologique, Campus Erasme, 1070 Bruxelles Belgium
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Marjorie FANJUL;
Marjorie FANJUL
‡Laboratoire de Biologie Cellulaire, UPS, rue des 36 Ponts, 31400 Toulouse, France
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Bruno ROUOT;
Bruno ROUOT
§INSERM U. 65, 34095 Montpellier, France
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Etienne HOLLANDE;
Etienne HOLLANDE
‡Laboratoire de Biologie Cellulaire, UPS, rue des 36 Ponts, 31400 Toulouse, France
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Nicole VAYSSE;
Nicole VAYSSE
*INSERM U. 151, CHU Rangueil, 31054 Toulouse cedex, France
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François CLEMENTE
François CLEMENTE
∥
*INSERM U. 151, CHU Rangueil, 31054 Toulouse cedex, France
∥To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 315 (2): 619–624.
Citation
Agnes ESTIVAL, Patrick ROBBERECHT, Marjorie FANJUL, Bruno ROUOT, Etienne HOLLANDE, Nicole VAYSSE, François CLEMENTE; Cells retrovirally transfected with fibroblast growth factor-2 isoforms exhibit altered adenylate cyclase activity and G-protein functionality. Biochem J 15 April 1996; 315 (2): 619–624. doi: https://doi.org/10.1042/bj3150619
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