PDGF dimer binds two receptors simultaneously

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Homo sapiens
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PDGF dimer binds two receptors simultaneously. The receptors dimerise on ligand binding and undergo conformational change which is key to receptor autophosphorylation (reviewed in Heldin et al, 1998). PDGFRA and PDGFRB activity can be inhibited by binding to type I and type II tyrosine kinase inhibitors (reviewed in Roskoski, 2018). Type I inhibitors such as crenolanib, avripatinib and pazopanib, bind to the active conformation of the receptor, while type II inhibitors like imatinib, sorafenib and others bind to the inactive conformation (Gril et al, 2013; Wang et al, 2014; Mathias et al, 2015; Meliau et al, 2017; Lombardo et al, 2004; Chen et al, 2006; Matsui et al, 2008; Liu et al, 2011; Hilberg et al, 2008; Hilberg et al, 2017; Wilhelm et al, 2002; Strumberg et al, 2005; Mendel et al, 2003; Roskoski, 2007). PDGFRA signaling can also be inhibited by the monoclonal antibody olaratumab, which interferes with binding of AA, BB and CC ligand to the receptor (Gerber et al, 2012; Loizos et al, 2005; Matei et al, 2006; Russell et al, 2010; Stock et al, 2007).

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