scholarly journals Novel Nuclear Signaling Pathway Mediates Activation of Fibroblast Growth Factor-2 Gene by Type 1 and Type 2 Angiotensin II Receptors

2001 ◽  
Vol 12 (2) ◽  
pp. 449-462 ◽  
Author(s):  
Hu Peng ◽  
John Moffett ◽  
Jason Myers ◽  
Xiaohong Fang ◽  
Ewa K. Stachowiak ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Nuclear Translocation ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Responsive Element

In bovine adrenal medullary cells synergistically acting type 1 and type 2 angiotensin II (AII) receptors activate the fibroblast growth factor-2 (FGF-2) gene through a unique AII-responsive promoter element. Both the type 1 and type 2 AII receptors and the downstream cyclic adenosine 1′,3′-monophosphate- and protein kinase C-dependent signaling pathways activate the FGF-2 promoter through a novel signal-transducing mechanism. This mechanism, which we have named integrative nuclear FGF receptor-1 signaling, involves the nuclear translocation of FGF receptor-1 and its subsequent transactivation of the AII-responsive element in the FGF-2 promoter.

Interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis and demonstration of FGF receptor expression in megakaryocytes and megakaryocytic-like cells

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1905-1913 ◽  
Author(s):  
A Bikfalvi ◽  
ZC Han ◽  
G Fuhrmann
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Hel Cells

Abstract We have investigated the interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis. Acidic FGF (aFGF) stimulated the proliferation of murine megakaryocytes and human erythroleukemia (HEL) cells in a concentration-dependent manner. The concentrations of aFGF required to elicit half-maximum and maximum effects were similar for HEL and megakaryocytic colony formation. The effect of aFGF was comparable to that of basic FGF (bFGF) in both cell types. The effect of both FGFs was found to be synergistic with interleukin-3 (IL-3), and was abrogated by a monoclonal anti-IL-6 antibody. A specific cell surface receptor complex of approximately 120 Kd was detected for FGF by crosslinking experiments on HEL cells and total bone marrow (BM) cells. Single-cell autoradiography of megakaryocytes in BM smears and BM cultures showed binding sites for 125I-aFGF. Northern blot analysis of messenger RNA (mRNA) from total BM and HEL cells showed a 4.4-kb mRNA specific for FGF receptors type 1 (flg) and type 2 (bek). This was confirmed by polymerase chain reaction, which also showed the presence of FGF receptor mRNA in megakaryocytic-like cells, normal megakaryocytes, and platelets. Together, these results indicate that FGF is involved in megakaryocytopoiesis and suggest that this interaction may be mediated via FGF receptor type 1 and type 2 located on the megakaryocytic lineage or on accessory cells responsible for the release of megakaryocytic growth-promoting activities.

scholarly journals Interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis and demonstration of FGF receptor expression in megakaryocytes and megakaryocytic-like cells

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1905-1913
Author(s):  
A Bikfalvi ◽  
ZC Han ◽  
G Fuhrmann
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Hel Cells

We have investigated the interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis. Acidic FGF (aFGF) stimulated the proliferation of murine megakaryocytes and human erythroleukemia (HEL) cells in a concentration-dependent manner. The concentrations of aFGF required to elicit half-maximum and maximum effects were similar for HEL and megakaryocytic colony formation. The effect of aFGF was comparable to that of basic FGF (bFGF) in both cell types. The effect of both FGFs was found to be synergistic with interleukin-3 (IL-3), and was abrogated by a monoclonal anti-IL-6 antibody. A specific cell surface receptor complex of approximately 120 Kd was detected for FGF by crosslinking experiments on HEL cells and total bone marrow (BM) cells. Single-cell autoradiography of megakaryocytes in BM smears and BM cultures showed binding sites for 125I-aFGF. Northern blot analysis of messenger RNA (mRNA) from total BM and HEL cells showed a 4.4-kb mRNA specific for FGF receptors type 1 (flg) and type 2 (bek). This was confirmed by polymerase chain reaction, which also showed the presence of FGF receptor mRNA in megakaryocytic-like cells, normal megakaryocytes, and platelets. Together, these results indicate that FGF is involved in megakaryocytopoiesis and suggest that this interaction may be mediated via FGF receptor type 1 and type 2 located on the megakaryocytic lineage or on accessory cells responsible for the release of megakaryocytic growth-promoting activities.

Fibroblast growth factor-2 stimulates phospholipase Cβ in adult cardiomyocytes

1999 ◽  
Vol 77 (6) ◽  
pp. 569-575 ◽  
Author(s):  
Paramjit S Tappia ◽  
Raymond R Padua ◽  
Vincenzo Panagia ◽  
Elissavet Kardami
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Isolated Heart ◽  
Second Messengers ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Hypertrophic Response ◽  
Adult Cardiomyocytes ◽  
G Protein Coupled

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.

Fibroblast Growth Factor-2 Mediates Angiotensin Ii-Induced Cardiac Hypertrophy in Renovascular Hypertension

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 683-683
Author(s):  
Corinne Pellieux ◽  
Alessandro Foletti ◽  
Thercse Sauthier ◽  
Aubert Jean-Francois ◽  
Beermann Friedrich ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Cardiac Hypertrophy ◽  
Fibroblast Growth Factor ◽  
Renovascular Hypertension ◽  
Intracellular Signaling ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Jnk Activation

29 In renovascular hypertension, angiotensin II leads to an elevation of blood pressure and to cardiac hypertrophy. The fibroblast growth factor-2 (FGF-2) has been implicated in cardiomyocyte growth. Therefore, we investigated whether FGF-2 could control the development of angiotensin II-induced cardiac hypertrophy. Mice deficient for the expression of FGF-2 were created, and the role of FGF-2 was investigated in the two kidney-one clip (2K1C) model of renin-dependent hypertension. The activation of the MAPK pathways were shown to be crucial in the intracellular signaling leading to cardiac hypertrophy. Therefore, we followed also the cardiac activation of JNK, ERK and the p38 kinase in these animals. Both wild-type and FGF-2 deficient (FGF-2 -/-) mice showed similar elevation of blood pressure in the 2K1C model. Interestingly, 2K1C FGF-2 -/- mice developed markedly reduced hypertrophy as compared to wild-types. Moreover, in 2K1C wild-types, cardiac hypertrophy developed in association with a concomitant stimulation of JNK, ERK and p38. In contrast, JNK activation was strongly decreased in hypertensive mice deficient for FGF-2, while p38 and ERK were less affected. These data suggest that FGF-2 is important in mediating angiotensin II-induced cardiac hypertrophy in renovascular hypertension via autocrine/paracrine mechanisms.

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

1999 ◽  
Vol 56 (3) ◽  
pp. 883-897 ◽  
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

Control of fibroblast growth factor receptor kinase signal transduction by heterodimerization of combinatorial splice variants

1993 ◽  
Vol 13 (7) ◽  
pp. 3907-3918
Author(s):  
E Shi ◽  
M Kan ◽  
J Xu ◽  
F Wang ◽  
J Hou ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Splice Variants ◽  
Sh2 Domain ◽  
Scatchard Analysis ◽  
Fibroblast Growth ◽  
Dose Dependent

A differentiated liver cell (HepG2), which exhibits a dose-dependent growth-stimulatory and growth-inhibitory response to heparin-binding fibroblast growth factor type 1 (FGF-1), displays high- and low-affinity receptor phenotypes and expresses specific combinatorial splice variants alpha 1, beta 1, and alpha 2 of the FGF receptor (FGF-R) gene (flg). The extracellular domains of the alpha and beta variants consist of three and two immunoglobulin loops, respectively, while the intracellular variants consist of a tyrosine kinase (type 1) isoform and a kinase-defective (type 2) isoform. The type 2 isoform is also devoid of the two major intracellular tyrosine autophosphorylation sites (Tyr-653 and Tyr-766) in the type 1 kinase. An analysis of ligand affinity, dimerization, autophosphorylation, and interaction with src homology region 2 (SH2) substrates of the recombinant alpha 1, beta 1, and alpha 2 isoforms was carried out to determine whether dimerization of the combinatorial splice variants might explain the dose-dependent opposite mitogenic effects of FGF. Scatchard analysis indicated that the alpha and beta isoforms exhibit low and high affinity for ligand, respectively. The three combinatorial splice variants dimerized in all combinations. FGF enhanced dimerization and kinase activity, as assessed by receptor autophosphorylation. Phosphopeptide analysis revealed that phosphorylation of Tyr-653 was reduced relative to phosphorylation of Tyr-766 in the type 1 kinase component of heterodimers of the type 1 and type 2 isoforms. The SH2 domain substrate, phospholipase C gamma 1 (PLC gamma 1), associated with the phosphorylated type 1-type 2 heterodimers but was phosphorylated only in preparations containing the type 1 kinase homodimer. The results suggest that phosphorylation of Tyr-653 within the kinase catalytic domain, but not Tyr-766 in the COOH-terminal domain, may be stringently dependent on a trans intermolecular mechanism within FGF-R kinase homodimers. Although phosphotyrosine 766 is sufficient for interaction of PLC gamma 1 and other SH2 substrates with the FGF-R kinase, phosphorylation and presumably activation of substrates require the kinase homodimer and phosphorylation of Tyr-653. We propose that complexes of phosphotyrosine 766 kinase monomers and SH2 domain signal transducers may constitute unactivated presignal complexes whose active or inactive fate depends on homodimerization with a kinase or heterodimerization with a kinase-defective monomer, respectively. The results suggest a mechanism for control of signal transduction by different concentrations of ligand through heterodimerization of combinatorial splice variants from the same receptor gene.

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