PDGF alpha- and beta-receptors activate unique and common signal transduction pathways.
We have examined the signal transduction pathways of the PDGF alpha- and beta-receptors, in order to characterize the specificity of each receptor type in the signaling. Porcine aortic endothelial cell lines expressing equal levels of either PDGF alpha- or beta-receptors were established. The alpha- and beta-receptor cells responded mitogenically to stimulation with the proper PDGF isoforms. Three aspects of actin reorganization were examined after ligand stimulation: loss of stress fibres, appearance of edge ruffles and formation of circular membrane ruffles. The beta-receptor cells showed a response to ligand stimulation which included all three features. The alpha-receptor cells exhibited edge ruffles and loss of stress fibres, but circular ruffles could not be found in several independent alpha-receptor cell lines. The beta-receptor cells, but not the alpha-receptor cells, were able to migrate chemotactically towards a concentration gradient of ligand. The molecular basis for the differences in signalling were explored by comparing the pattern of increased phosphorylation of potential substrates for the alpha- and beta-receptors in [32P]orthophosphate labelled intact cells and using an in vitro kinase assay. Certain of the observed substrates were common for the two receptors, whereas others were specific for either one. We conclude that certain of the known PDGF induced cellular effects are transduced only by the beta-receptor; the presence of alpha-receptor-specific substrates suggests that there are also alpha-receptor-specific signals, which have yet to be identified.
Eriksson
A
A
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Siegbahn
A
A
Westermark
B
B
Heldin
C H
CH
Claesson-Welsh
L
L
D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010710:Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D013552:Swine; D014162:Transfection
D000199:Actins; D010710:Phosphates; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D011494:Protein Kinases; D017479:Receptors, Platelet-Derived Growth Factor