Platelet-derived growth factor-AA (PDGF-AA)

Platelet-derived growth factor-AA (PDGF-AA) is a homodimeric glycoprotein consisting of two A subunits, serving as a key ligand in the PDGF/VEGF signaling family [1, 20]. It is primarily synthesized and stored in the alpha-granules of platelets, from which it is released upon injury to stimulate tissue repair and wound healing [1, 18]. PDGF-AA functions by binding with high affinity to the Platelet-derived growth factor receptor alpha (PDGFR-alpha), inducing receptor dimerization and activating intracellular signaling pathways such as PI3K/Akt and MAPK/ERK [3, 21]. These pathways drive the proliferation, migration, and survival of mesenchymal cells, including fibroblasts, smooth muscle cells, and glial cells [1, 3]. In addition to its physiological roles in development and repair, dysregulated PDGF-AA signaling is a hallmark of several pathological conditions, including various malignancies like glioblastoma and osteosarcoma, as well as fibrotic and vascular diseases [2, 9, 12]. Therapeutic intervention typically targets the PDGF-AA/PDGFR-alpha axis using small-molecule tyrosine kinase inhibitors such as imatinib and sunitinib, or monoclonal antibodies like olaratumab, to disrupt autocrine and paracrine growth loops in tumors and fibrotic tissues [2, 8, 23].

Other names

PDGF-A homodimerPlatelet-derived growth factor subunit A homodimerGlioma-derived growth factorOsteosarcoma-derived growth factor

Platelet-derived growth factor-AA (PDGF-AA) acts as a ligand that binds specifically to the Platelet-derived growth factor receptor alpha (PDGFR-alpha) homodimer or the PDGFR-alpha/beta heterodimer [3, 10, 21]. This binding triggers receptor dimerization and autophosphorylation of tyrosine residues in the cytoplasmic domain, initiating downstream signaling through the PI3K/Akt, MAPK/ERK, and PLC-gamma pathways to regulate cell growth, survival, and motility [3, 10, 21].