The proteins of the PDGF family consist of several disulfide- bonded dimeric isoforms: PDGFAA, PDGF-AB, PDGF-BB, PDGF-CC and PDGF-DD, which bind in a distinct pattern to two highly related RTKs: PDGFR-a and PDGFR-b. PDGFR-a and PDGFR-b show 85% and 75% identity between the two intracellular kinase domains, but the kinase insert and carboxy terminal tail regions display only 27% and 28% identity. PDGFR-a binds all PDGF isoforms except PDGF-D, whereas PDGFR-b can only affiliate with PDGF-B and D 1). PDGFR-a and PDGFR-b not only form homo- and heterodimers, but also dimerize with EGFR, which can be stimulated by PDGF (2). The total number and the ratio of receptor subunits expressed varies between cell types, possibly accounting for the variable responsiveness of different cell types to PDGF (3). Ligand binding induces receptor dimerization and autophosphorylation, allowing binding and activation of cytoplasmic SH2 domain- containing signal transduction molecules including Grb2, Src, GAP, PI3 kinase, PLCg and Nck. A number of different signaling pathways are thereby initiated leading to cell growth, actin reorganization, migration and differentiation (4). Tyr751 in the kinase-insert region of PDGFR-b is the docking site for PI3 kinase 5). Phosphorylated pentapeptides derived from Tyr751 of PDGFR-b (pTyr751-Val-Pro-Met-Leu) inhibit the association of the carboxy-terminal SH2 domain of the p85 subunit of PI3 kinase with PDGFR-b (6). Tyr740 is also required for PDGFR-b- mediated PI-3 kinase activation 7).