THE 4TH IMMUNOGLOBULIN DOMAIN OF THE STEM-CELL FACTOR-RECEPTOR COUPLES LIGAND-BINDING TO SIGNAL-TRANSDUCTION

Receptor dimerization is ubiquitous to the action of all receptor tyro sine kinases, and in the case of dimeric ligands, such as the stem cel l factor (SCF), it was attributed to ligand bivalency. However, by usi ng a dimerization-inhibitory monoclonal antibody to the SCF receptor, we confined a putative dimerization site to the nonstandard fourth imm unoglobulin-like domain of the receptor. Deletion of this domain not o nly abolished ligand-induced dimerization and completely inhibited sig nal transduction, but also provided insights into the mechanism of the coupling of ligand binding to dimer formation. These results identify an intrinsic receptor dimerization site and suggest that similar site s may exist in other receptors.