THE ALPHA-PDGFR TYROSINE KINASE MEDIATES LOCOMOTION OF 2 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 expre ssing 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, suggestin g that cell migration observed in 32D expressing alpha RWT is mainly d ue to alpha PDGFR-mediated chemotaxis. Consistent with these results, PDGF-AA induced significant cell migration of NTH3T3 fibroblasts, whic h was markedly blocked by the presence of excess neutralizing polyclon al antibody to PDGF-AA. These results provide evidence that alpha PDGF R kinase activity is essential for mediating ligand-induced chemotacti c and chemokinetic responses in two different cell types. (C) 1994 Aca demic Press, Inc.