The platelet derived growth factor receptor (PDGFR) has been implicated in multiple cellular processes including membrane ruffling, chemotaxis and mitogenesis. The PDGFRs form a dimeric complex upon receptor binding leading to auto-phosphorylation of tyrosine residues within the cytoplasmic tail of the receptor. These phosphotyrosines function as binding sites for multiple SH2 domain containing enzymes and adapters. The activation of these effectors results in a signaling cascade leading to cellular responses. A useful approach to dissect the role of these effector molecules in a cellular process is by removing the binding sites for the majority of the effector molecules and adding them back one at a time to measure their contribution to a cellular process. Work on the betaPDGFR has uncovered a role for the tyrosines which recruit phoshatidylinositol 3-kinase (PI3K) in PDGF dependent DNA synthesis and cellular transformation. In experiments to establish the requirement for PI3K in PDGF dependent DNA synthesis, the PI3K inhibitors wortmannin and LY249002 at sufficient doses to inhibit PI3K activity were unable to inhibit PDGF-dependent DNA synthesis when added at early time points (0-60 minutes) post PDGF stimulation. These PI3K inhibitors were able to efficiently inhibit the DNA synthesis response when added at later time points (4-8 hours). These data have led to the testable hypothesis that PDGF-dependent DNA synthesis requires PI3K activity not immediately after PDGF stimulation but at a later time, approximately 4-6 hours post stimulation. If this hypothesis is correct it suggests that the early peak of PI3K products may be essential for other cellular process such as membrane ruffling and chemotaxis.