FGF-2 dimerization involvement in growth factor mediated cell proliferation but not cell differentiation.
Dimerization is a prerequisite for many growth factors in their receptor activation leading to cellular response. FGF-1 and FGF-2, members of the Fibroblast Growth Factor (FGF) family, were shown to form non-covalent dimers and oligomers in vitro. Using the two-hybrid system as an in vivo binding assay we show here that of three representative members of the FGF family, only FGF-2 is able to homodimerize. Moreover the FGF-2 isoforms could heterodimerize. Two single-point mutants (T121F and W123R), defective in their dimerization capability, were isolated through random mutagenesis and were used to study the role of FGF-2 dimerization with regard to its biological activity. Remarkably, these mutant proteins were still able to induce cell differentiation, but were strongly affected in their capacity to promote cell proliferation. This study thus highlights the uncoupling between proliferation and differentiation FGF-2 signaling pathways and the crucial role of FGF-2 dimerization in the mitogenic activity of this factor.
Van den Berghe
L
L
Laboratoire de Biologie Moléculaire Eucaryote du CNRS, Université Paul Sabatier, 118 Route de Narbonne, Toulouse Cedex, 31 062, France.
Mortier
I
I
Zanibellato
C
C
Amalric
F
F
Prats
H
H
Bugler
B
B
D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D019281:Dimerization; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006493:Heparin / Q000378:metabolism; D016296:Mutagenesis; D016716:PC12 Cells; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D006493:Heparin; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2