The alpha PDGFR tyrosine kinase mediates locomotion of two different cell types through chemotaxis and chemokinesis.
To determine the capability of alpha PDGFR to couple with chemotactic signaling, we established 32D cells expressing wild type alpha PDGFR (alpha RWT), a kinase-defective mutant of alpha PDGFR (alpha R627R), or wild type beta PDGFR (beta RWT). Using a modified Boyden chamber, we showed that PDGF induced significant cell migration of 32D cells expressing alpha RWT or beta RWT, but not of those expressing alpha R627R. Furthermore, the cell migration was largely reduced in each case when the same concentration of PDGF was present in both chambers, suggesting that cell migration observed in 32D expressing alpha RWT is mainly due to alpha PDGFR-mediated chemotaxis. Consistent with these results, PDGF-AA induced significant cell migration of NIH3T3 fibroblasts, which was markedly blocked by the presence of excess neutralizing polyclonal antibody to PDGF-AA. These results provide evidence that alpha PDGFR kinase activity is essential for mediating ligand-induced chemotactic and chemokinetic responses in two different cell types.
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
A
A
Uren
J C
JC
Yu
N S
NS
Gholami
J H
JH
Pierce
M A
MA
Heidaran
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor