Artificial control of subtype-specific platelet-derived growth factor-receptor signaling.
Platelet-derived growth factor (PDGF) signaling controls various physiological functions via two receptor subtypes: PDGF receptor (PDGFR) alpha and PDGFRbeta. Nevertheless, our understanding of their roles is limited because of a lack of pharmacological tools to discriminate subtype-specific signaling. We developed a chimeric receptor by combining ligand-binding-domain truncated PDGFRbeta with anti-fluorescein single chain antibody, expecting the control of PDGFRbeta-specific signaling by oligomerized fluorescein as an artificial agonist. Results show that calcium mobilization, Cdc42 activation, and cell migration were elicited specifically by the artificial ligand in cells expressing the chimeric receptor. Our method is expected to be useful to understand the subtype-specific roles of PDGFRs in various cellular functions.
Isa
Masayuki
M
Department of Neurobiology, Graduate School of Medicine, The University of Tokyo, Japan.
Ohta
Yusaku
Y
Namiki
Shigeyuki
S
Hirose
Kenzo
K
D000595:Amino Acid Sequence; D020013:Calcium Signaling / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005452:Fluoresceins; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D050506:Mutant Chimeric Proteins / Q000187:drug effects / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D005452:Fluoresceins; D008024:Ligands; D050506:Mutant Chimeric Proteins; D017479:Receptors, Platelet-Derived Growth Factor; D020764:cdc42 GTP-Binding Protein