Effects of Platelet-Derived Growth Factor on Degradation,Nuclear Translocation of Nonhistone Proteins,and DNA Synthesis

Abstract

Abstract

Stimulation of resting normal rat kidney fibroblasts, prelabeled with [³H]leucine, by platelet-derived growth factor (PDGF) caused inhibition of cellular protein degradation and a parallel increased nuclear translocation of ³H-labeled nonhistone proteins (³H-NHP) and DNA synthesis. Nuclear translocation of these proteins was independent of protein synthesis. Fractionation of the nuclear ³H-NHP in a pH gradient of 2.5–6.5 showed that the protein fractions with a high degree of proteolysis in resting cells corresponded to the protein fractions with a high extent of translocation in stimulated cells, suggesting that degradation and translocation of these proteins may be related. PDGF inhibited cellular uptake of [³H]chloroquine, suggesting that PDGF inhibits NHP degradation via the lysosomal pathway. These observations support the hypothesis that PDGF induces NHP translocation to the nucleus by inhibiting lysosomal degradation of these proteins.