Different effects of homo- and heterodimers of platelet-derived growth factor A and B chains on human and mouse fibroblasts.
Binding sites for platelet-derived growth factor (PDGF) differ in their selectivity for the AA, AB and BB forms of PDGF. Human fibroblasts bind BB well and AA poorly, whereas Swiss 3T3 cells bind more similar quantities of each ligand. We found that AA PDGF was weakly mitogenic for human fibroblasts, but strongly mitogenic for 3T3 cells. Tyrosine phosphorylation of human fibroblast receptors was stimulated most by BB and least by AA, whereas the phosphorylation of 3T3 cell receptors was stimulated more uniformly by the three dimers. The receptor polypeptides that were phosphorylated were very similar. We suggest that phosphorylation of the receptor is proportional to the number of binding sites available for each ligand. Tyrosine phosphorylation of a number of other cell proteins was also proportional to receptor phosphorylation. In contrast, protein kinase C (PKC)-dependent serine and tyrosine phosphorylations were stimulated maximally by low level occupancy of PDGF binding sites, and phosphorylation of p36 required high occupancy. These data raise the possibility that differences in biological potency of AA, AB and BB forms of PDGF may be due simply to differences in the numbers of binding sites, rather than to different biochemical functions of their receptors.
Kazlauskas
A
A
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Bowen-Pope
D
D
Seifert
R
R
Hart
C E
CE
Cooper
J A
JA
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D066298:In Vitro Techniques; D007526:Isoelectric Point; D051379:Mice; D008970:Molecular Weight; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D019000:Phosphotyrosine; D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C