Effects of platelet-derived growth factor on degradation, nuclear translocation of nonhistone proteins, and DNA synthesis.
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.
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Department of Pathology, College of Medicine, University of Illinois, Chicago 60612.
D000818:Animals; D001692:Biological Transport; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D002738:Chloroquine / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D008247:Lysosomes / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D010982:Platelet-Derived Growth Factor; D011506:Proteins; D002738:Chloroquine; D004247:DNA; D003513:Cycloheximide