Differential requirement of a motif within the carboxyl-terminal domain of α-platelet-derived growth factor (αPDGF) receptor for PDGF focus forming activity chemotaxis, or growth

Abstract

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 αPDGF receptor (αR) containing a series of deletion or point mutations. The ability of fms/αR 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 αPDGFR 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 Cγ. Therefore, our findings suggest that: (i) the focus forming function of αPDGFR correlates well with the ability of the receptor to bind phospholipase Cγ, and (ii) the mechanism of focus formation mediated by αPDGFR may be distinguished from that required for chemotaxis or anchorage-independent growth.