Platelet-derived growth factor (PDGF) is produced as four distinct polypeptide monomers that dimerize to become the active form. Five different active forms can be secreted by various cell types, including endothelial cells, epithelial cells, and Kupffer cells. Upon binding of PDGFR, a receptor tyrosine kinase expressed as two distinct homodimers or a heterodimer, a number of signaling pathways can be initiated. PI3K activation and the Akt pathway can be triggered to result in NF-κB translocation to the nucleus, JAK-STAT signaling can activate STAT transcription factors, and RAS GTPase signaling activates AP-1 (c-Jun and c-Fos) transcription factors. PDGF can therefore stimulate cell proliferation as well as inflammation, and has been associated with diseases such as hepatic fibrosis and cancer.
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