Translocation of protein kinase C-delta by PDGF in cultured vascular smooth muscle cells: inhibition by TGF-beta 1.
The migration and proliferation of vascular smooth muscle cells (SMC) into the neointima are important early events in the development of atherosclerosis and post-angioplasty restenosis. The stimulation of SMC migration by platelet derived growth factor (PDGF) involves the induction of protein kinase C activity. Using immunoblot techniques, we demonstrated that rat aortic SMC express a pattern of PKC isoforms which includes PKC-alpha, delta, epsilon, zeta and eta. Upon exposure to PDGF-BB, a fraction of PKC-delta was rapidly translocated from the cytosol to the post-nuclear particulate fraction at 15 seconds and reached an apparent maximum at 30 minutes. In contrast, PKC-alpha and zeta were not translocated by PDGF-BB, TGF-beta 1, which inhibits PDGF-induced DNA synthesis and chemotaxis, reduced the immunoreactive levels of PKC-delta and blocked the PDGF-induced translocation of PKC-delta to the particulate fraction. This suggests that the activation of PKC-delta by translocation to the particulate fraction may play an important role in the control of vascular smooth muscle cell migration by PDGF and TGF-beta 1.
Leng
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L
Department of Medicine, Cornell University Medical College, New York, NY 10021, USA.
Du
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B
Consigli
S
S
McCaffrey
T A
TA
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001013:Aorta, Thoracic; D000077214:Becaplermin; D002478:Cells, Cultured; D015151:Immunoblotting; D007527:Isoenzymes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051745:Protein Kinase C-delta; D020574:Proto-Oncogene Proteins c-sis; D011817:Rabbits; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000906:Antibodies; D007527:Isoenzymes; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D000077214:Becaplermin; C497260:Prkcd protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta