A novel monoclonal antibody dependent on domain 5 of the platelet-derived growth factor beta receptor inhibits ligand binding and receptor activation.
Platelet derived growth factor (PDGF) induces activation of the protein tyrosine kinase domain of the PDGF receptor, resulting in receptor dimerization and the initiation of mitogenesis in responsive cells. In order to identify domains of the receptor involved in these processes, a panel of monoclonal antibodies (MAbs) against the extracellular region of the human PDGF receptor was developed and screened to identify which of these specifically block PDGF binding. One of these, MAb 2A1E2, binds PDGF beta receptor with high affinity and blocks PDGF BB binding in a whole cell binding assay with an IC 50 of 0.1 nM. Inhibition of binding results in the inhibition of ligand-induced receptor phosphorylation, dimerization and mitogenesis in cells expressing the PDGF beta receptor. MAb 2A1E2 has been mapped to the fifth Ig domain of the PDGF beta receptor, implying that this domain is important for ligand binding, dimerization and/or activation. The potency of MAb 2A1E2 for inhibiting PDGF BB binding indicates that this antibody is ideally suited to identify and characterize PDGF BB-induced biological responses.
Ramakrishnan
V
V
COR Therapeutics, Inc., South San Francisco, CA 94080.
Escobedo
M A
MA
Fretto
L J
LJ
Seroogy
J J
JJ
Tomlinson
J E
JE
Wolf
D L
DL
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001483:Base Sequence; D001667:Binding, Competitive; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D010982:Platelet-Derived Growth Factor; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor