title: Membrane display and functional analysis of juxtacrine ligand-receptor signaling.
abstract: We developed a strategy for identifying modulators of juxtacrine signaling, triggered by a cell-surface ligand displayed on synthetic lipid bilayers, via cognate receptors on apposed cells. Using readouts for receptor lateral transport and intracellular signaling, we screened a small interfering RNA (siRNA) library and identified specific receptor tyrosine kinases (RTKs) that directly or indirectly modulate apoptosis signaling by a model death ligand through its cognate death receptors. This approach may be broadly useful for studying juxtacrine cell-cell signaling systems.
authors.affiliation: Cancer Immunology, Genentech, Inc, South San Francisco, CA.
authors.forename: Pradeep M
authors.initials: PM
authors.lastname: Nair
authors.affiliation: Pathology, Genentech, Inc, South San Francisco, CA.
authors.forename: Hai
authors.initials: H
authors.lastname: Ngu
authors.affiliation: Biochemical and Cellular Pharmacology, Genentech, Inc, South San Francisco, CA.
authors.forename: Eric
authors.initials: E
authors.lastname: Torres
authors.affiliation: Cancer Immunology, Genentech, Inc, South San Francisco, CA.
authors.forename: Scot
authors.initials: S
authors.lastname: Marsters
authors.affiliation: Cancer Immunology, Genentech, Inc, South San Francisco, CA.
authors.forename: David A
authors.initials: DA
authors.lastname: Lawrence
authors.affiliation: Biochemical and Cellular Pharmacology, Genentech, Inc, South San Francisco, CA.|Servier, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Stephan
authors.affiliation: Pathology, Genentech, Inc, South San Francisco, CA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Komuves
authors.affiliation: Cancer Immunology, Genentech, Inc, South San Francisco, CA.
authors.forename: Avi
authors.initials: A
authors.lastname: Ashkenazi
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002450:Cell Communication / Q000235:genetics*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D008051:Lipid Bilayers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics; D053218:Receptors, Death Domain / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; D034741:RNA, Small Interfering; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand
keywords: apoptosis; caspase; death receptor; juxtacrine; screen; supported membrane display; transport