The research will investigate how platelet derived growth factor (PDGF) brings about the initiation of cell proliferation. In order to understand normal growth control and transformation it is important to determine the mechanism whereby a mitogenic polypeptide binds receptors and thereafter changes gene expression. When density-arrested BALB/c-3T3 cells were incubated with PDGF there was a rapid stimulation of a unique phosphoprotein. This phosphoprotein has a molecular weight of 180,000 daltons and data indicates it may be the PDGF receptor. This system thus may allow the study of the cell biology of the PDGF stimulated kinase believed to be the PDGF receptor. This 180K phosphoprotein will be compared to the receptor associated phosphoprotein observed after PDGF addition to isolated plasma membranes. The PDGF stimulated kinase activity will be correlated to the PDGF binding capacity of the receptor during traverse of the cell cycle. The half-life of the PDGF stimulated kinase activity will be compared to the PDGF binding. These studies will demonstrate if both activities are in the same molecule and if they are coordinately regulated. Studies are designed to indicate if the PDGF stimulated kinase has other cellular substrates and effects the cellular events whereby PDGF activates gene expression. The effects of PDGF stimulated kinase activity on the EGF receptor will be determined. We will determine the involvement of the PDGF inducible protein, CpI (29,000 MW), in the initiation of growth. CpI and anti-CpI antibodies will be used to determine CpI involvement in proliferation. These reagents (CpI and antibodies) will be used to assay stimulation of proliferation and to investigate possible cellular events leading to growth (as determined by CpI synthesis). Since transformation alters PDGF requirement it is important to understand how PDGF functions. This information may lead to the elucidation of how a neoplastic event arises. (J)
| Olashaw, N E; Kusmik, W; Daniel, T O et al. (1991) Biochemical and functional discrimination of platelet-derived growth factor alpha and beta receptors in BALB/c-3T3 cells. J Biol Chem 266:10234-40 |
| Drozdoff, V; Pledger, W J (1991) Cellular response to platelet-derived growth factor (PDGF)-AB after down-regulation of PDGF alpha-receptors. Evidence that functional binding does not require alpha-receptors. J Biol Chem 266:17165-72 |
| Cheung, H S; Mitchell, P G; Pledger, W J (1989) Induction of expression of c-fos and c-myc protooncogenes by basic calcium phosphate crystal: effect of beta-interferon. Cancer Res 49:134-8 |
