Receptor phenotype underlies differential response of hepatocytes and nonparenchymal cells to heparin-binding fibroblast growth factor type 1 (aFGF) and type 2 (bFGF)

1992 ◽  
Vol 28 (7-8) ◽  
pp. 515-520 ◽  
Author(s):  
Mikio Kan ◽  
Guo-Chen Yan ◽  
Jianming Xu ◽  
Mitsuru Nakahara ◽  
Jinzhao Hou
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Differential Response ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Nonparenchymal Cells ◽  
Factor Type ◽  
Receptor Phenotype

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.

scholarly journals Fibroblast Growth Factor Type 2 (FGF2) Administration Attenuated the Clinical Manifestations of Preeclampsia in a Murine Model Induced by L-NAME

2021 ◽  
Vol 12 ◽  
Author(s):  
Margarita L Martinez-Fierro ◽  
Gloria Patricia Hernadez-Delgadillo ◽  
Jose Feliciano Flores-Mendoza ◽  
Claudia Daniela Alvarez-Zuñiga ◽  
Martha Lizeth Diaz-Lozano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Murine Model ◽  
Clinical Manifestations ◽  
Histological Evaluation ◽  
Growth Delay ◽  
Hypertensive Disorder ◽  
Fibroblast Growth ◽  
Factor Type

Background: In preeclampsia, a hypertensive disorder of pregnancy, the poor remodeling of spiral arteries leads to placental hypoperfusion and ischemia, provoking generalized maternal endothelial dysfunction and, in severe cases, death. Endothelial and placental remodeling is important for correct pregnancy evolution and is mediated by cytokines and growth factors such as fibroblast growth factor type 2 (FGF2). In this study, we evaluated the effect of human recombinant FGF2 (rhFGF2) administration in a murine model of PE induced by NG-nitro-L-arginine methyl ester (L-NAME) to test if rhFGF2 administration can lessen the clinical manifestations of PE.Methods: Pregnant rats were administrated with 0.9% of NaCl (vehicle), L-NAME (60 mg/kg), FGF2 (666.6 ng/kg), L-NAME+FGF2 or L-NAME + hydralazine (10 mg/kg) from the 10th to 19th days of gestation. Blood pressure (BP), urine protein concentrations and anthropometric values both rat and fetuses were assessed. Histological evaluation of organs from rats delivered by cesarean section was carried out using hematoxylin and eosin staining.Results: A PE-like model was established, and it included phenotypes such as maternal hypertension, proteinuria, and fetal growth delay. Compared to the groups treated with L-NAME, the L-NAME + FGF2 group was similar to vehicle: the BP remained stable and the rats did not develop enhanced proteinuria. Both the fetuses and placentas from rats treated with L-NAME + FGF2 had similar values of weight and size compared with the vehicle.Conclusion: The intravenous administration of rhFGF2 showed beneficial and hypotensive effects, reducing the clinical manifestations of PE in the evaluated model.

Fgfr2 and osteopontin domains in the developing skull vault are mutually exclusive and can be altered by locally applied FGF2

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3375-3384 ◽  
Author(s):  
S. Iseki ◽  
A.O. Wilkie ◽  
J.K. Heath ◽  
T. Ishimaru ◽  
K. Eto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Coronal Suture ◽  
Fibroblast Growth ◽  
Skull Vault ◽  
Fgfr2 Gene ◽  
Factor Type

Mutations in the human fibroblast growth factor receptor type 2 (FGFR2) gene cause craniosynostosis, particularly affecting the coronal suture. We show here that, in the fetal mouse skull vault, Fgfr2 transcripts are most abundant at the periphery of the membrane bones; they are mutually exclusive with those of osteopontin (an early marker of osteogenic differentiation) but coincide with sites of rapid cell proliferation. Fibroblast growth factor type 2 (FGF2) protein, which has a high affinity for the FGFR2 splice variant associated with craniosynostosis, is locally abundant; immunohistochemical detection showed it to be present at low levels in Fgfr2 expression domains and at high levels in differentiated areas. Implantation of FGF2-soaked beads onto the fetal coronal suture by ex utero surgery resulted in ectopic osteopontin expression, encircled by Fgfr2 expression, after 48 hours. We suggest that increased FGF/FGFR signalling in the developing skull, whether due to FGFR2 mutation or to ectopic FGF2, shifts the cell proliferation/differentiation balance towards differentiation by enhancing the normal paracrine down-regulation of Fgfr2.

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 Fibroblast Growth Factor Type 2 Signaling Is Critical for DNA Repair in Human Keratinocyte Stem Cells

Stem Cells ◽  
2010 ◽  
Vol 28 (9) ◽  
pp. 1639-1648 ◽  
Author(s):  
Ghida Harfouche ◽  
Pierre Vaigot ◽  
Walid Rachidi ◽  
Odile Rigaud ◽  
Sandra Moratille ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Repair ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Human Keratinocyte ◽  
Factor Type ◽  
Keratinocyte Stem Cells
Sign in / Sign up

Export Citation Format

Share Document