scholarly journals Platelet-Derived Growth Factor-Receptor α Strongly Inhibits Melanoma Growth In Vitro and In Vivo

Neoplasia ◽  
2009 ◽  
Vol 11 (8) ◽  
pp. 732-W7 ◽  
Author(s):  
Debora Faraone ◽  
Maria Simona Aguzzi ◽  
Gabriele Toietta ◽  
Angelo M. Facchiano ◽  
Francesco Facchiano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Melanoma Growth

scholarly journals Sustained Platelet-Derived Growth Factor Receptor α Signaling in Osteoblasts Results in Craniosynostosis by Overactivating the Phospholipase C-γ Pathway

2008 ◽  
Vol 29 (3) ◽  
pp. 881-891 ◽  
Author(s):  
Anne Moenning ◽  
Richard Jäger ◽  
Angela Egert ◽  
Wolfram Kress ◽  
Eva Wardelmann ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Bone Matrix ◽  
Growth Factor Receptor ◽  
Specific Inhibitor ◽  
Platelet Derived Growth Factor ◽  
Cranial Sutures ◽  
First Time

ABSTRACT The development and growth of the skull is controlled by cranial sutures, which serve as growth centers for osteogenesis by providing a pool of osteoprogenitors. These osteoprogenitors undergo intramembranous ossification by direct differentiation into osteoblasts, which synthesize the components of the extracellular bone matrix. A dysregulation of osteoblast differentiation can lead to premature fusion of sutures, resulting in an abnormal skull shape, a disease called craniosynostosis. Although several genes could be linked to craniosynostosis, the mechanisms regulating cranial suture development remain largely elusive. We have established transgenic mice conditionally expressing an autoactivated platelet-derived growth factor receptor α (PDGFRα) in neural crest cells (NCCs) and their derivatives. In these mice, premature fusion of NCC-derived sutures occurred at early postnatal stages. In vivo and in vitro experiments demonstrated enhanced proliferation of osteoprogenitors and accelerated ossification of osteoblasts. Furthermore, in osteoblasts expressing the autoactivated receptor, we detected an upregulation of the phospholipase C-γ (PLC-γ) pathway. Treatment of differentiating osteoblasts with a PLC-γ-specific inhibitor prevented the mineralization of synthesized bone matrix. Thus, we show for the first time that PDGFRα signaling stimulates osteogenesis of NCC-derived osteoblasts by activating the PLC-γ pathway, suggesting an involvement of this pathway in the etiology of human craniosynostosis.

scholarly journals Platelet-Derived Growth Factor Receptor-β Constitutive Activity Promotes Angiogenesis In Vivo and In Vitro

2007 ◽  
Vol 27 (10) ◽  
pp. 2142-2149 ◽  
Author(s):  
Peetra U. Magnusson ◽  
Camilla Looman ◽  
Aive Åhgren ◽  
Yan Wu ◽  
Lena Claesson-Welsh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Constitutive Activity

scholarly journals Bidirectional Signaling Links the Abelson Kinases to the Platelet-Derived Growth Factor Receptor

2004 ◽  
Vol 24 (6) ◽  
pp. 2573-2583 ◽  
Author(s):  
Rina Plattner ◽  
Anthony J. Koleske ◽  
Andrius Kazlauskas ◽  
Ann Marie Pendergast
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Nonreceptor Tyrosine Kinase ◽  
Membrane Ruffling ◽  
Bidirectional Signaling ◽  
Β Receptor

ABSTRACT The c-Abl nonreceptor tyrosine kinase is activated by growth factor signals such as the platelet-derived growth factor (PDGF) and functions downstream of the PDGF-β receptor (PDGFR) to mediate biological processes such as membrane ruffling, mitogenesis, and chemotaxis. Here, we show that the related kinase Arg is activated downstream of PDGFRs in a manner dependent on Src family kinases and phospholipase C γ1 (PLC-γ1)-mediated phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis, as we showed previously for c-Abl. PIP2, a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits the tyrosine kinase activities of both Arg and c-Abl in vitro and in cells. We now demonstrate that c-Abl and Arg form inducible complexes with and are phosphorylated by the PDGFR tyrosine kinase in vitro and in vivo. Moreover, c-Abl and Arg, in turn, phosphorylate the PDGFR. We show that c-Abl and Arg exhibit nonredundant functions downstream of the activated PDGFR. Reintroduction of c-Abl into Arg-Abl double-null fibroblasts rescues the ability of PLC-γ1 to increase PDGF-mediated chemotaxis, while reexpression of Arg fails to rescue the chemotaxis defect. These data show that, although both kinases are activated and form complexes with proteins in the PDGFR signaling pathway, only c-Abl functions downstream of PLC-γ1 to mediate chemotaxis.

scholarly journals Platelet-Derived Growth Factor Receptor β But Not α Mediates Cardiac Fibrosis In Vitro and In Vivo

2017 ◽  
Vol 26 ◽  
pp. S142
Author(s):  
B. Wang ◽  
J. Liu ◽  
Y. Hua ◽  
L. Huang ◽  
K. Huang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cardiac Fibrosis ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor

scholarly journals Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4720-4730 ◽  
Author(s):  
Amber N. Stratman ◽  
Amy E. Schwindt ◽  
Kristine M. Malotte ◽  
George E. Davis
Keyword(s):  
Growth Factor ◽  
Basement Membrane ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Heparin Binding ◽  
Matrix Assembly ◽  
Matrix Deposition ◽  
Membrane Matrix

Recently, we reported a novel system whereby human pericytes are recruited to endothelial cell (EC)–lined tubes in 3-dimensional (3D) extracellular matrices to stimulate vascular maturation including basement membrane matrix assembly. Through the use of this serum-free, defined system, we demonstrate that pericyte motility within 3D collagen matrices is dependent on the copresence of ECs. Using either soluble receptor traps consisting of the extracellular ligand-binding domains of platelet-derived growth factor receptor β, epidermal growth factor receptor (EGFR), and ErbB4 receptors or blocking antibodies directed to platelet-derived growth factor (PDGF)–BB, or heparin-binding EGF-like growth factor (HB-EGF), we show that both of these EC-derived ligands are required to control pericyte motility, proliferation, and recruitment along the EC tube ablumenal surface. Blockade of pericyte recruitment causes a lack of basement membrane matrix deposition and, concomitantly, increased vessel widths. Combined inhibition of PDGF-BB and HB-EGF–induced signaling in quail embryos leads to reduced pericyte recruitment to EC tubes, decreased basement membrane matrix deposition, increased vessel widths, and vascular hemorrhage phenotypes in vivo, in support of our findings in vitro. In conclusion, we report a dual role for EC-derived PDGF-BB and HB-EGF in controlling pericyte recruitment to EC-lined tubes during developmental vascularization events.

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