title: Selection of multiple agonist antibodies from intracellular combinatorial libraries reveals that cellular receptors are functionally pleiotropic.
abstract: The main purpose of this perspective is to build on the unexpected outcomes of previous laboratory experiments using antibody agonists to raise questions concerning how activation of a given receptor can be involved in inducing differentiation of cells along different pathways some of which may even derive from different lineages. While not yet answered, the question illustrates how the advent of agonists not present in nature may give a different dimension to the important problem of signal transduction. Thus, if one studies a natural agonist-receptor system one can learn details about its signal transduction pathway. However, if one has a set of orthogonal agonists, one may learn about the yet undiscovered potential of the system that, in the end, may necessitate refinements to the currently used models. Thus, we wonder why receptors conventionally linked to a given pathway induce a different pattern of differentiation when agonized in another way.
authors.affiliation: Shanghai Institute for Advanced Immunological Studies, ShanghaiTech University, Shanghai 200031, China.
authors.forename: Kyungmoo
authors.initials: K
authors.lastname: Yea
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: rlerner@scripps.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lerner
mesh_terms: D000906:Antibodies / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D000070819:Discoidin Domain Receptor 1; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D000075386:Netrin Receptors; D019151:Peptide Library; D015202:Protein Engineering; D020794:Receptor Protein-Tyrosine Kinases / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000906:Antibodies; D000075386:Netrin Receptors; D019151:Peptide Library; D011956:Receptors, Cell Surface; D054852:Small Molecule Libraries; C115727:UNC5C protein, human; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases