The a platelet derived growth factor receptor (aPDGFR) extracellular Immunoglobulin (Ig) like domains 1 ± 3 contain major determinants for ligand interaction. We now report that a deletion of Ig-like loop 3, but not Iglike loop 1 or 2, of the aPDGFR causes ligandindependent transformation in NIH3T3 cells. Biochemical analyses of aPDGFR mutants lacking Ig-like loop 3 indicate that cellular transformation is mediated by ligand-independent activation of the aPDGFR tyrosine kinase activity as determined by receptor autophosphorylation both in vivo and in vitro. Moreover, crosslinking analysis of aPDGFR mutants expressed ectopically in NIH3T3 cells indicate that deletion within extracellular domain 3 leads to ligand-independent receptor dimerization. All of these ®ndings suggest that the Ig-like loop 3 of the aPDGFR contains the major determinants which inhibit receptor dimerization in the quiescent cells and that the ligand binding induces receptor activation by neutralizing the inhibitory e ect of this domain.
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