To determine the molecular basis for the transforming function of platelet-derived growth factor (PDGF)-A in NIH/3T3 cells, we have constructed chimerae consisting of the extracellular domain of the human CSF-1R (fms) linked to the cytoplasmic domain of the PDGF receptor (R) containing a series of deletion or point mutations. The ability of fms/R chimerae to mediate CSF-1-dependent anchorage-independent growth, focus formation, and chemotaxis of NIH/3T3 cells was then examined. Our results provide evidence that a domain encompassing amino acid residues 977-1024 of the PDGFR is required for ligand-dependent focus formation, but not chemotaxis or anchorage-independent growth, and that tyrosine residues within this domain constitute the major binding site for phospholipase C. Therefore, our findings suggest that: (i) the focus forming function of PDGFR correlates well with the ability of the receptor to bind phospholipase C, and (ii) the mechanism of focus formation mediated by PDGFR may be distinguished from that required for chemotaxis or anchorage-independent growth.

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