Platelet-derived growth-factor receptor PDGFR

Board, R. and Jayson, G. 2005. Platelet-derived growth factor receptor (PDGFR) a target for anti cancer therapeutics. Drug Resistance Updates 8(1-2), 75-83. 

Platelet-derived growth factor receptor (PDGFR)... 

Imatinib (STI571) is an inhibitor of the tyrosine kinase domain of the Bcr-Abl oncoprotein and prevents the phosphorylation of the kinase substrate by ATP. It is indicated for the treatment of chronic myelogenous leukemia (CML), a pluripotent hematopoietic stem cell disorder characterized by the t(9 22) Philadelphia chromosomal translocation. This translocation results in the Bcr-Abl fusion protein, the causative agent in CML, and is present in up to 95% of patients with this disease. This agent inhibits other activated receptor tyrosine kinases for platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF), and c-kit. 

Platelet-Derived Growth Factor Receptor (PDGFR). 137... 

The structure of the N-SHP-2 SH2 domain in complex with peptides based on the platelet-derived growth factor receptor (PDGFR) and the adapter protein IRSl revealed that the interaction between the protein and the peptide is extended to the residue 5 positions C-terminal to the pTyr (Lee et al., 1994). In these structures, the +3 position binding pocket is opened in order to create such an extended interface. The interactions between the peptide and the protein are primarily hydro-phobic. For example, a Phe at the +5 position of the IRSl peptide binds between the EF and BG loops and interacts with the He at the +3 position (Lee et al., 1994). Other than this extended interface, the interactions in this structure are reminiscent of those observed in the Src SH2 domain structure the peptide binds in an extended conformation perpendicular to the central (3-sheet. 

---