The fourth immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction.
Receptor dimerization is ubiquitous to the action of all receptor tyrosine kinases, and in the case of dimeric ligands, such as the stem cell factor (SCF), it was attributed to ligand bivalency. However, by using a dimerization-inhibitory monoclonal antibody to the SCF receptor, we confined a putative dimerization site to the nonstandard fourth immunoglobulin-like domain of the receptor. Deletion of this domain not only abolished ligand-induced dimerization and completely inhibited signal 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 sites may exist in other receptors.
Blechman
J M
JM
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Lev
S
S
Barg
J
J
Eisenstein
M
M
Vaks
B
B
Vogel
Z
Z
Givol
D
D
Yarden
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004789:Enzyme Activation; D018604:Epitope Mapping; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D012995:Solubility; D019089:Stem Cell Factor
D000911:Antibodies, Monoclonal; D016298:Hematopoietic Cell Growth Factors; D008024:Ligands; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases