Platelet Derived Growth Factor (PDGF) is a mitogen for mesenchyme- and glia-derived cells. PDGF consists of two chains, A and B, which dimerize to form functionally distinct isoforms, PDGF-AA, PDGF-AB, and PDGF-BB. These three isoforms bind with different affinities to two receptor types, a and b, which are endowed with protein tyrosine kinase domains and undergo either homo- or heterodimerization as a consequence of ligand binding. Ligand stimulation of PDGFR-b leads to autophosphorylation at Tyr-857, which is the major autophosphorylation site, and Tyr-751, which is the major in vitro phosphorylation site. Autophosphorylation of Tyr-751, which lies in the kinase insert region, is required for binding of phosphatidylinositol-3 kinase to the receptor. These auto-phosphorylation events largely contribute to signal transduction through the PDGF receptor. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.