Independent expression of human alpha or beta platelet-derived growth factor receptor cDNAs in a naive hematopoietic cell leads to functional coupling with mitogenic and chemotactic signaling pathways.
Distinct genes encode alpha and beta platelet-derived growth factor (PDGF) receptors that differ in their abilities to be triggered by three dimeric forms of the PDGF molecule. We show that PDGF-receptor mitogenic function can be reconstituted in a naive hematopoietic cell line by introduction of expression vectors for either alpha or beta PDGF receptor cDNAs. Thus, each receptor is independently capable of coupling with mitogenic signal-transduction pathways inherently present in these cells. Activation of either receptor also resulted in chemotaxis, alterations in inositol lipid metabolism, and mobilization of intracellular Ca2+. The magnitude of these functional responses correlated well with the binding properties of the different PDGF isoforms to each receptor. Thus, availability of specific PDGF isoforms and relative expression of each PDGF-receptor gene product are major determinants of the spectrum of known PDGF responses.
Matsui
T
T
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Pierce
J H
JH
Fleming
T P
TP
Greenberger
J S
JS
LaRochelle
W J
WJ
Ruggiero
M
M
Aaronson
S A
SA
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002633:Chemotaxis; D004247:DNA / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D005796:Genes; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection
D007377:Interleukin-3; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor