Platelet-derived Growth Factor (PDGF) Signaling Pathway

Platelet-Derived Growth Factor (PDGF) Signaling Network

Platelet-derived growth factor (PDGF) signaling network consists of four ligands, PDGFA-D, and two receptors, PDGFRalpha and PDGFRbeta. All PDGFs function as secreted, disulphide-linked homodimers, but only PDGFA and B can form functional heterodimers.

Mechanism of Platelet-Derived Growth Factor (PDGF) Signaling Pathway

The four PDGF ligands-PDGFA-D are inactive in their monomeric forms. The PDGFs bind to the protein tyrosine kinase receptors PDGFRA and PDGFRB. These two receptor isoforms dimerize upon binding the PDGF dimer, leading to three possible receptor combinations, namely -AA, -BB and -AB. Dimerization can cause the activation of the kinase. Kinase activation is visualized as tyrosinephosphorylation of the receptor molecules, which occurs between the dimerized receptor molecules (transphosphorylation). In conjunction with dimerization and kinase activation, the receptor molecules undergo conformational changes, which allow a basal kinase activity to phosphorylate a critical tyrosineresidue, thereby "unlocking" the kinase, leading to full enzymatic activity directed toward other tyrosine residues in the receptor molecules as well as other substrates for the kinase.

Mechanism of Platelet-Derived Growth Factor (PDGF) Signaling Pathway

Fig 3. Platelet-Derived Growth Factor (PDGF) Signaling Pathway

Platelet-Derived Growth Factor (PDGF) Signaling Function

Platelet-derived growth factor receptor (PDGFR) signaling plays a crucial role in specifying mesenchymal stem cell (MSC) commitment to mesenchymal lineages. Platelet-derived growth factor signaling critically regulates postinfarction repair. Both PDGFR-β– and PDGFR-α–mediated pathways promote collagen deposition in the infarct. Activation of PDGF-B/PDGFR-β is also involved in recruitment of mural cells by neovessels, regulating maturation of the infarct vasculature. Acquisition of a mural coat and matura.

Inhibition of Platelet-derived Growth Factor Receptor (PDGFR) Signaling

Inhibition of the PDGF signal pathway results in loss of pericytes and a reduction in vessel density in the neovascularized cornea that correlates with reduced expression of PDGF, ang1/2, and VEGF mRNA. PI3-K is known to be involved in the regulation of VEGF, ang1, and PDGF, as the PI3-K inhibitors wortmannin or LY294002 has similar effects. Since PDGF is a known stimulus for PI3-K activation, decrease in VEGF, ang1/2, and PDGF mRNA levels on administration of the PDGF inhibitor is caused by the decreased activation of the PI3-K signaling cascade.

Platelet-derived Growth Factor (PDGF) Signaling Pathway Related Studies

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