Platelet-Derived Growth Factor Isoforms AA,AB,and BB Differentially Activate Poly r(I):r(C)-Induced Genes in Human Fibroblast FS4 Cells

Polyribocytidylic-polyriboinosinic acid [poly r(I):r(C)]-inducible genes were isolated by a differential screening procedure from a human fibroblast cell (FS-4) cDNA bank. Among yet unidentified genes (gene 274), one codes for a protein with multiple finger motifs and has previously been detected in endothelial cells after tumor necrosis factor-α (TNF-α) treatment (A20; Opipari et al., 1990), the second one codes for a variant of the IxB family (Haskill et al., 1991), and a third one for the Ca²⁺ ATPase (isoform 1). Platelet-derived growth factor (PDGF) isoforms (AA, AB, and BB) stimulated the expression of these immediate-early genes. But the extent of the respective induction correlated neither with the number of the two receptors α or β nor with the level of PDGF-stimulated receptor autophosphorylation on tyrosine. Although α-receptors were less abundant than β-receptors (12,500 binding sites were estimated for PDGF-AA, K_D 0.03 nM; 20,000 for PDGF-AB, K_D 0.03 nM; 35,000 for PDGF-BB K_D 0.16 nM) and tyrosine phosphorylation induced by PDGF-AA was significantly less than that evoked by PDGF-BB, some of the investigated genes were more strongly induced by PDGF-AA. We discuss how the differences in the biological potency of the PDGF isoforms may reside in different functions of the two receptors by activation of alternative signaling pathways.