Role of nuclear protein kinase C in the mitogenic response to platelet-derived growth factor.
We have assessed the involvement of nuclear envelope protein phosphorylation in the mitogenic response to platelet-derived growth factor (PDGF) in NIH/3T3 fibroblasts. We find that stimulation of quiescent NIH/3T3 cells with PDGF or with the mitogenic protein kinase C (PKC) activators phorbol 12-myristate 13-acetate (PMA) or bryostatin 1 (bryo) leads to rapid, dose-dependent phosphorylation of several nuclear envelope polypeptides. The predominant nuclear envelope targets for mitogen-induced phosphorylation are immunologically identified as the nuclear envelope lamins. All three lamin species (A, B and C) are phosphorylated in response to PMA or bryo, while lamins A and C are preferentially phosphorylated in response to PDGF. Phosphopeptide mapping and phosphoamino acid analysis indicate that similar serine sites on the lamins are phosphorylated in response to PDGF, PMA and bryo. Both mitogenicity and lamina phosphorylation induced by these mitogens can be inhibited by the selective PKC inhibitor staurosporine at 2 nM. Treatment of quiescent NIH/3T3 cells with PDGF, PMA or bryo leads to rapid translocation of PKC to the nuclear envelope. These data indicate that rapid nuclear events, including translocation of cytosolic PKC to the nuclear membrane and lamina phosphorylation, may play a role in the transduction of the mitogenic signals of PDGF from the cytoplasm to the nucleus in NIH/3T3 fibroblasts.
Fields
A P
AP
Johns Hopkins Oncology Center, Baltimore, Maryland 21231.
Tyler
G
G
Kraft
A S
AS
May
W S
WS
D000818:Animals; D054713:Bryostatins; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D034882:Lamins; D018942:Macrolides; D008934:Mitogens / Q000494:pharmacology; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D054713:Bryostatins; D007783:Lactones; D034882:Lamins; D018942:Macrolides; D008934:Mitogens; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; C046785:bryostatin 1; D012694:Serine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate