Platelet-derived growth factor mechanisms

Kanter P, Leister KJ, Tomei LD, Wenner PA, Wenner CE (1984) Epidermal growth factor and tumor promoters prevent DNA fragmentation by different mechanisms. Biochem Biophys Res Commun 118 392-399 Kariya K-I, Kawahara Y, Tsuda T (1987) Possible involvement of protein kinase C in platelet-derived growth factor-stimulated DNA synthesis in vascular smooth musde cells. Atherosderosis 83 251-255... 

Mechanism of Action A platelet-derived growth factor that heals open wounds. Therapeutic Effect Stimulates body to grow new tissue. 

Imatinib is an inhibitor of the protein tyrosine kinase involved with platelet-derived growth factor (Bcr-ABL). A loss of cellular control of this tyrosine kinase has been identified as a key mechanism for malignant cell growth. The ability of imatinib to inhibit Bcr-ABL provides a rationale for its use in the treatment of human cancers such as Philadelphia... 

The insulin receptor is the prototype for a number of receptor enzymes with a similar structure and receptor Tyr kinase activity. The receptors for epidermal growth factor and platelet-derived growth factor, for example, have structural and sequence similarities to the insulin receptor, and both have a protein Tyr kinase activity that phosphorylates IRS-1. Many of these receptors dimerize after binding ligand the insulin receptor is already a dimer before insulin binds. The binding of adaptor proteins such as Grb2 to (P) Tyr residues is a common mechanism for promoting protein-protein interactions, a subject to which we return in Section 12.5. 

Among the coumarins isolated from species of Artemisia (Asteraceae), esculetin (6,7-dihydroxycoumarin) and its dimethyl-ether scoparone were known to be antiproliferative on vascular smooth muscle cells. This activity was further found in some very simple mono-substituted coumarins, which were even more potent than esculetin, although less effective. In an attempt to verify its mechanism of action, esculetin was tested for interactions with PTK and PKC. The induction of membrane PTK activity by either foetal calf serum or platelet-derived growth factor (PDGF) was moderately reduced by esculetin, whereas no effect was observed against PKC [56]. 

Larson, O., Latham, C., Zickert, P. and Zetterbetg, A. (1989). Cell cycle regulation of human diploid fibroblasts possible mechanisms of platelet derived growth factor. J. Cell. Physiol. 139, 477-483. 

Jun N-terminal kinases (JNKl and JNK2) were activated in response to cannabinoid receptor agonists in CHO cells expressing recombinant CBi receptors, and this was mediated through a pathway that included Gi/o, PI3K and Ras (Rueda et al. 2000). In the CHO cells (a fibroblast cell line), the transactivation of platelet-derived growth factor receptor was implicated in the JNK activation mechanism (Rueda et al. 2000). 

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