DIFFERENTIAL REQUIREMENT OF A MOTIF WITHIN THE CARBOXYLTERMINAL DOMAIN OF ALPHA-PLATELET-DERIVED GROWTH-FACTOR (ALPHA-PDGF) RECEPTOR FOR PDGF FOCUS-FORMING ACTIVITY CHEMOTAXIS, OR GROWTH

To determine the molecular basis for the transforming function of plat elet derived growth factor (PDGF)-A in NIH/3T3 cells, we have construc ted chimerae consisting of the extracellular domain of the human CSF-1 R (fms) linked to the cytoplasmic domain of the alpha PDGF receptor (a lpha R) containing a series of deletion or point mutations. The abilit y of fms/alpha R chimerae to mediate CSF-l-dependent anchorage-indepen dent growth, focus formation, and chemotaxis of NIH/3T3 cells was then examined. Our results provide evidence that a domain encompassing ami no acid residues 977-1024 of the alpha PDGFR is required for ligand-de pendent focus formation, but not chemotaxis or anchorage-independent g rowth, and that tyrosine residues within this domain constitute the ma jor binding site for phospholipase C gamma. Therefore, our findings su ggest that: (i) the focus forming function of alpha PDGFR correlates w ell with the ability of the receptor to bind phospholipase C gamma, an d (ii) the mechanism of focus formation mediated by (alpha PDGFR may b e distinguished from that required for chemotaxis or anchorage-indepen dent growth.