Peptides derived from specific interaction sites of the fibroblast growth factor 2 - FGF receptor complexes induce receptor activation and signaling

Although fibroblast growth factor-2 (FGF-2) plays an important role in cardioprotection and growth, little is known about the signals triggered by it in the adult heart. We therefore examined FGF-2-induced effects on phosphoinositide-specific phospholipase C (PI-PLC) isozymes, which produce second messengers linked to the inotropic and hypertrophic response of the myocardium. FGF-2, administered by retrograde perfusion to the isolated heart, induced an increase in inositol-1,4,5-trisphosphate levels in the cytosol, as well as an increase in total PI-PLC activity associated with sarcolemmal and cytosolic fractions. Furthermore FGF-2 induced a time-dependent elevation in cardiomyocyte membrane-associated PLC gamma1 and PLC β1 activities, assayed in immunoprecipitated fractions, and moreover, increased the membrane levels of PLC β1 and PLC β3. Activation of PLC β is suggestive of FGF-2-induced cross-talk between FGF-receptor tyrosine kinase and G-protein-coupled signaling in adult cardiomyocytes and underscores the importance of FGF-2 in cardiac physiology.Key words: FGF-2, signal transduction, PLC gamma, PLC β, cardiomyocytes.

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Fibroblast growth factor-2 (FGF-2) and FGF-receptor (FGFR-1) immunoreactivity in embryonic spinal autonomic neurons

Cell and Tissue Research ◽

10.1007/s004410050771 ◽

1997 ◽

Vol 287 (3) ◽

pp. 471-480 ◽

Cited By ~ 9

Author(s):

Christian Stapf ◽

Gabriele Lück ◽

Mehdi Shakibaei ◽

Dieter Blottner

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Fgf Receptor ◽

Autonomic Neurons

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Differential effects of fibroblast growth factor (FGF) 9 and FGF2 on proliferation, differentiation and terminal differentiation of chondrocytic cells in vitro

Biochemical Journal ◽

10.1042/bj3420677 ◽

1999 ◽

Vol 342 (3) ◽

pp. 677-682 ◽

Cited By ~ 28

Author(s):

Nicole B. WEKSLER ◽

Gregory P. LUNSTRUM ◽

Eric S. REID ◽

William A. HORTON

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Physiological Responses ◽

Terminal Differentiation ◽

Receptor Activation ◽

Fibroblast Growth ◽

Fgf Receptor ◽

Chondrocytic Differentiation ◽

Mitotic Inhibitor

Fibroblast growth factor (FGF) 9 was compared with FGF2 in its ability to influence proliferation, differentiation, terminal differentiation and apoptosis in a rat calvaria-derived cell line (RCJ 3.1C5.18) that spontaneously undergoes chondrocyte differentiation in vitro. Like FGF2, FGF9 promoted proliferation, but to a lesser extent. In contrast to FGF2, which blocked chondrocytic differentiation, FGF9 had no effect on differentiation but inhibited terminal differentiation. FGF9 also stimulated expression of the mitotic inhibitor p21 to a greater extent than FGF2. Neither ligand influenced apoptosis. The results indicate that FGF9 could account for many of the physiological responses attributed to FGF-receptor activation in the growth plate.

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Localization of fibroblast growth factor-2 (basic FGF) and FGF receptor-1 in adult human kidney11See Editorial by Barasch, p. 1156.

Kidney International ◽

10.1046/j.1523-1755.1999.00637.x ◽

1999 ◽

Vol 56 (3) ◽

pp. 883-897 ◽

Cited By ~ 30

Author(s):

Jürgen Floege ◽

Kelly L. Hudkins ◽

Frank Eitner ◽

Yan Cui ◽

Richard S. Morrison ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Fgf Receptor ◽

Basic Fgf ◽

Adult Human

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Polarizing receptor activation dissociates fibroblast growth factor 2 mediated inhibition of myelination from its neuroprotective potential

Acta Neuropathologica Communications ◽

10.1186/s40478-019-0864-6 ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 4

Author(s):

Katja Thümmler ◽

Eran Rom ◽

Thomas Zeis ◽

Maren Lindner ◽

Sarah Brunner ◽

...

Keyword(s):

Multiple Sclerosis ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Neurological Diseases ◽

Receptor Activation ◽

Fibroblast Growth ◽

Fgf Receptor ◽

Neuroprotective Signaling ◽

Mechanistic Basis ◽

Novel Strategy

AbstractFibroblast growth factor (FGF) signaling contributes to failure of remyelination in multiple sclerosis, but targeting this therapeutically is complicated by its functional pleiotropy. We now identify FGF2 as a factor up-regulated by astrocytes in active inflammatory lesions that disrupts myelination via FGF receptor 2 (FGFR2) mediated activation of Wingless (Wnt) signaling; pharmacological inhibition of Wnt being sufficient to abrogate inhibition of myelination by FGF2 in tissue culture. Using a novel FGFR1-selective agonist (F2 V2) generated by deleting the N-terminal 26 amino acids of FGF2 we demonstrate polarizing signal transduction to favor FGFR1 abrogates FGF mediated inhibition of myelination but retains its ability to induce expression of pro-myelinating and immunomodulatory factors that include Cd93, Lif, Il11, Hbegf, Cxcl1 and Timp1. Our data provide new insights into the mechanistic basis of remyelination failure in MS and identify selective activation of FGFR1 as a novel strategy to induce a neuroprotective signaling environment in multiple sclerosis and other neurological diseases.

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