The expression of PDGF-alpha but not PDGF-beta receptors is suppressed in Swiss/3T3 fibroblasts over-expressing protein kinase C-alpha.
The generation and characterization of Swiss/3T3 cells which stably over-express protein kinase C (PKC)-alpha were previously described by us. In these cells over-expression of PKC-alpha reduced the expression of epidermal growth factor (EGF) receptor molecules [(1990) J. Biol. Chem. 265, 13290-13296]. Here we show that the expression of PDGF-alpha receptors, but not PDGF-beta receptors, was specifically decreased in these cells. Not only were the levels of PDGF-alpha receptor mRNA transcript and protein significantly diminished in the PKC-alpha over-producing cells, but their ability to respond to short- and long-term growth factor signals was appropriately compromised. This was reflected in a reduced tyrosine autophosphorylation signal in response to PDGF-AA, as well as in decreased growth rates of PKC-alpha over-expressing cells when supplied with external PDGF-AA. A similar decrease in PDGF-alpha receptors was also demonstrated in parental Swiss/3T3 cells treated with phorbol esters. Our studies imply that PKC-alpha is involved in a cellular mechanism suppressing the expression of PDGF-alpha receptors in Swiss/3T3 cells. Hence, activation of PKC-alpha or alterations in its cellular levels may affect, in turn, the expression of a specific set of cell surface receptors and their responses to external growth factors.
Fitzer-Attas
C
C
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Eldar
H
H
Eisenbach
L
L
Livneh
E
E
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate