Preliminary in vitro and in vivo investigation of a potent platelet derived growth factor receptor (PDGFR) family kinase inhibitor

2018 ◽  
Vol 28 (10) ◽  
pp. 1781-1784 ◽  
Author(s):  
Elizabeth A. Wilson ◽  
Wade A. Russu ◽  
Hassan M. Shallal
Keyword(s):  
Growth Factor ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor

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 Sphingosine-1-phosphate induces the migration and angiogenesis of EPCs through the Akt signaling pathway via sphingosine-1-phosphate receptor 3/platelet-derived growth factor receptor-β

2015 ◽  
Vol 20 (4) ◽  
Author(s):  
Hang Wang ◽  
Ke-Yin Cai ◽  
Wei Li ◽  
Hao Huang
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Akt Signaling ◽  
Platelet Derived Growth Factor ◽  
Akt Signaling Pathway ◽  
Akt Inhibitor ◽  
Sphingosine 1 Phosphate

AbstractEndothelial progenitor cells (EPCs) play a fundamental role in neoangiogenesis and tumor angiogenesis. Through the sphingosine-1-phosphate receptor 3 (S1PR3), sphingosine-1-phosphate (S1P) can stimulate the functional capacity of EPCs. Platelet-derived growth factor receptor-beta (PDGFR-β) contributes to the migration and angiogenesis of EPCs. This study aimed to investigate whether S1P induces the migration and angiogenesis of EPCs through the S1PR3/PDGFR-β/Akt signaling pathway. We used the Transwell system and the Chemicon In Vitro Angiogenesis Assay Kit with CAY10444 (an S1PR3 antagonist), AG1295 (a PDGFR kinase inhibitor) and sc-221226 (an Akt inhibitor) to examine the role of the S1PR3/PDGFR-β/Akt pathway in the S1Pinduced migration and angiogenesis of EPCs.

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.

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