Both homodimeric isoforms of PDGF (AA and BB) have mitogenic and chemotactic activity and stimulate phosphoinositol turnover

Abstract

Platelet-derived growth factor (PDGF) occurs as three dimeric isoforms, AA, BB, and AB, which were previously shown to bind to two receptors with different isoform-specificity, the A/B-type (binds all three isoforms) and the B-type (binds only PDGF-BB). Results from competition binding experiments with Swiss 3T3 cells suggest the existence of a third receptor type, which recognizes PDGF-AB and PDGF-BB. Furthermore, Swiss 3T3 cells and human dermal fibroblasts express different relative and absolute levels of these receptor types. In particular, Swiss 3T3 cells express 90,000 PDGF-AA binding sites (A/B-receptors) per cell, whereas human fibroblasts express only 20,000 A/B-receptors per cell. All three PDGF isoforms were tested in either cell type for their effect on DNA synthesis. PDGF-BB and PDGF-AA were also tested in Swiss 3T3 cells for their effect on inositol phospholipid metabolism and chemotaxis. Each isoform promoted all three processes dose-dependently, but there were differences in the maximum cellular responses elicited. These responses reflect the capacity of the cells to bind the individual isoforms. These results demonstrate that the previous distinctions in responsiveness to the different PDGF isoforms are primarily a consequence of the differences in the levels of surface expression of the various isoform-specific receptor types, rather than of the differences in the intrinsic activity of these isoforms. Furthermore, these results suggest that all types of PDGF receptors are capable of responding to their respective ligands by mediating phosphoinositide breakdown, chemotactic responses, and DNA synthesis. Whether they exhibit other functional differences remains to be seen.

Disruption of PDGFRα-initiated PI3K activation and migration of somite derivatives leads to spina bifida

“…Although the PDGFR␤ seems to consistently promote cell motility in multiple cell types, the ability of PDGFR␣ to regulate chemotaxis has proven to be a cell type-dependent phenomenon (reviewed by Ronnstrand and Heldin, 2001). In some cells, such as NIH and Swiss 3T3 cells, PDGFR␣ stimulation induces cell motility (Hosang et al, 1989;Rosenkranz et al, 1999), whereas in endothelial and vascular smooth muscle cells, PDGFR␣ activation represses migratory signals from other receptors (Koyama et al, 1992;Yokote et al, 1996). Our results suggest a primary role for the PDGFR␣ in promoting migration of this somite-derived population.…”

Guidance of mesoderm cell migration in theXenopusgastrula requires PDGF signaling

“…Westermark et al, 1990;Kundra et al, 1994;Hansen et al, 1996;Ronnstrand et al, 1999), and PDGFRα promotes a chemotactic response at least in some cells (e.g. Hosang et al, 1989;Ferns et al, 1990;Rosenkranz et al, 1999;Yu et al, 2001), although probably through a different mechanism (for reviews, see Hayashi et al, 1995;Ronnstrand and Heldin, 2001). A great deal of work on PDGF-stimulated chemotaxis relates to cultured cells in vitro.…”

Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts.

“…PDGF-AA and PDGF-BB are potent mitogens and chemoattractants when the responding cells possess both PDGFRa and PDGF-Rf (36). On the other hand, a number of cell types including smooth muscle cells (6), dermal fibroblasts (37), and RLF possess mainly PDGF-Rf.…”