PROTEIN-PHOSPHORYLATION IN RESPONSE TO PDGF STIMULATION IN CULTURED NEURONS AND ASTROCYTES

Platelet-derived growth factor (PDGF) is an important growth factor fo r a variety of cells, including neurons and glial cells. PDGF signal t ransduction pathways have been studied primarily in mesenchyme-derived cells (such as fibroblasts and smooth muscle cells). However, little is known about these pathways in the central nervous system (CNS). It is believed that phosphorylation is a critical aspect of several steps in the signal transduction pathway. In this study, neurons and type 1 astrocytes in vitro were radiolabeled with P-32-orthophosphate (P-32- P-i). The cells were lysed, and labeled proteins were separated by two -dimensional gel electrophoresis. Autoradiograms of PDGF-stimulated an d control samples were compared. We found that in neurons and type 1 a strocytes in vitro, PDGF-BB greatly enhances protein phosphorylation w hile PDGF-AA has less of an effect on protein phosphorylation. Further more, because PDGF signal transduction pathways are likely to affect t he cytoskeleton, we studied changes in actin-binding proteins induced by PDGF-BB. We found that PDGF-BB alters the expression, migration pat tern and/or avidity of some actin-binding proteins in neurons. In conc lusion, protein phosphorylation is up-regulated by PDGF in mouse corti cal neurons and type 1 astrocytes in vitro. PDGF's effects on phosphor ylation of cytoskeletal proteins might be a important mechanism by whi ch PDGF affects the development and normal functions of central nervou s system cells. (C) 1997 Elsevier Science B.V.