scholarly journals Soluble dominant-negative receptor uncovers essential roles for fibroblast growth factors in multi-organ induction and patterning

1998 ◽  
Vol 17 (6) ◽  
pp. 1642-1655 ◽  
Author(s):  
G. Celli
Keyword(s):  
Growth Factors ◽  
Fibroblast Growth Factors ◽  
Dominant Negative ◽  
Fibroblast Growth

scholarly journals Fibroblast Growth Factors Regulate Prolactin Transcription via an Atypical Rac-Dependent Signaling Pathway

2003 ◽  
Vol 17 (10) ◽  
pp. 1921-1930 ◽  
Author(s):  
Twila A. Jackson ◽  
David M. Koterwas ◽  
Melissa A. Morgan ◽  
Andrew P. Bradford
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Signaling Pathway ◽  
Promoter Activity ◽  
Fibroblast Growth Factors ◽  
Dominant Negative ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Fibroblast Growth ◽  
Prl Gene

Abstract Fibroblast growth factors (FGFs) play a critical role in pituitary development and in pituitary tumor formation and progression. We have previously characterized FGF signal transduction and regulation of the tissue-specific rat prolactin (rPRL) promoter in GH4 pituitary cells. FGF induction of rPRL transcription is independent of Ras, but mediated by a protein kinase C-δ (PKCδ)-dependent activation of MAPK (ERK). Here we demonstrate a functional role for the Rho family monomeric G protein, Rac1, in FGF regulation of PRL gene expression via an atypical signaling pathway. Expression of dominant negative Rac, but not RhoA or Cdc42, selectively inhibited FGF-induced rPRL promoter activity. Moreover, expression of dominant negative Rac also attenuated FGF-2 and FGF-4 stimulation of MAPK (ERK). However, in contrast to other Rac-dependent signaling pathways, FGF activation of rPRL promoter activity was independent of the c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase/Akt cascades. FGFs failed to activate JNK1 or JNK2, and expression of dominant negative JNK or Akt constructs did not block FGF-induced PRL transcription. Consistent with the role of PKCδ in FGF regulation of PRL gene expression, activation of the rPRL promoter was blocked by an inhibitor of phospholipase Cγ (PLCγ) activity. FGF treatment also induced rapid tyrosine phosphorylation of PLCγ in a Rac-dependent manner. These results suggest that FGF-2 and FGF-4 activate PRL gene expression via a novel Rac1, PLCγ, PKCδ, and ERK cascade, independent of phosphoinositol-3-kinase and JNK.

Fibroblast Growth Factor Activation of the Rat PRL Promoter is Mediated by PKCδ

2001 ◽  
Vol 15 (9) ◽  
pp. 1517-1528
Author(s):  
Twila A. Jackson ◽  
Rebecca E. Schweppe ◽  
David M. Koterwas ◽  
Andrew P. Bradford
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Map Kinase ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factors ◽  
Enzyme Activation ◽  
Dominant Negative ◽  
Pituitary Cells ◽  
Fibroblast Growth ◽  
Pkc Inhibitors

Abstract Fibroblast growth factors play a critical role in cell growth, development, and differentiation and are also implicated in the formation and progression of tumors in a variety of tissues including pituitary. We have previously shown that fibroblast growth factor activation of the rat PRL promoter in GH4T2 pituitary tumor cells is mediated via MAP kinase in a Ras/Raf-1-independent manner. Herein we show using biochemical, molecular, and pharmacological approaches that PKCδ is a critical component of the fibroblast growth factor signaling pathway. PKC inhibitors, or down-regulation of PKC, rendered the rat PRL promoter refractory to subsequent stimulation by fibroblast growth factors, implying a role for PKC in fibroblast growth factor signal transduction. FGFs caused specific translocation of PKCδ from cytosolic to membrane fractions, consistent with enzyme activation. In contrast, other PKCs expressed in GH4T2 cells (α, βI, βII, andε ) did not translocate in response to fibroblast growth factors. The PKCδ subtype-selective inhibitor, rottlerin, or expression of a dominant negative PKCδ adenoviral construct also blocked fibroblast growth factor induction of rat PRL promoter activity, confirming a role for the novel PKCδ isoform. PKC inhibitors selective for the conventional α and β isoforms or dominant negative PKCα adenoviral expression constructs had no effect. Induction of the endogenous PRL gene was also blocked by adenoviral dominant negative PKCδ expression but not by an analogous dominant negative PKCα construct. Finally, rottlerin significantly attenuated FGF-induced MAP kinase phosphorylation. Together, these results indicate that MAP kinase-dependent fibroblast growth factor stimulation of the rat PRL promoter in pituitary cells is mediated by PKCδ.

Cytogenetics, Immunostaining for Fibroblast Growth Factors, p53 Sequencing, and Clinical Features of Two Cases of Cystosarcoma Phyllodes

2000 ◽  
Vol 5 (3) ◽  
pp. 179-190 ◽  
Author(s):  
PAUL V. WOOLLEY ◽  
SUSANNE M. GOLLIN ◽  
WAHEEB RISKALLA ◽  
SYDNEY FINKELSTEIN ◽  
DAVID F. STEFANIK ◽  
...  
Keyword(s):  
Growth Factors ◽  
Clinical Features ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Cystosarcoma Phyllodes

Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications

2019 ◽  
Vol 20 (8) ◽  
pp. 852-870
Author(s):  
Hassan Dianat-Moghadam ◽  
Ladan Teimoori-Toolabi
Keyword(s):  
Growth Factors ◽  
Wound Repair ◽  
Fibroblast Growth Factors ◽  
Predictive Biomarkers ◽  
Fibroblast Growth ◽  
Loss Of Function ◽  
Cellular Processes ◽  
Fgfr Signaling ◽  
Proliferation And Metastasis ◽  
Immense Potential

Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger a variety of cellular processes including angiogenesis, evasion from apoptosis, bone formation, embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation, cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore, gain-of-function or loss-of-function in FGFRs1-4 which is due to amplification, fusions, mutations, and changes in tumor–stromal cells interactions, is associated with the development and progression of cancer. Although, the developed small molecule or antibodies targeting FGFR signaling offer immense potential for cancer therapy, emergence of drug resistance, activation of compensatory pathways and systemic toxicity of modulators are bottlenecks in clinical application of anti-FGFRs. In this review, we present FGF/FGFR structure and the mechanisms of its function, as well as cross-talks with other nodes and/or signaling pathways. We describe deregulation of FGF/FGFR-related mechanisms in human disease and tumor progression leading to the presentation of emerging therapeutic approaches, resistance to FGFR targeting, and clinical potentials of individual FGF family in several human cancers. Additionally, the underlying biological mechanisms of FGF/FGFR signaling, besides several attempts to develop predictive biomarkers and combination therapies for different cancers have been explored.

An Overview on Fibroblast Growth Factors: Structural, Functional and Therapeutic Implications

2015 ◽  
Vol 12 (3) ◽  
pp. 144-151 ◽  
Author(s):  
Vidyalatha Kolli ◽  
Subhankar Paul ◽  
Nandini Sarkar
Keyword(s):  
Growth Factors ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Therapeutic Implications

scholarly journals Acidic and basic fibroblast growth factors stimulate tyrosine kinase activity in vivo.

1988 ◽  
Vol 263 (2) ◽  
pp. 988-993 ◽  
Author(s):  
S R Coughlin ◽  
P J Barr ◽  
L S Cousens ◽  
L J Fretto ◽  
L T Williams
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Tyrosine Kinase Activity
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