A fully human inhibitory monoclonal antibody to the Wnt receptor RYK.
RYK is an unusual member of the receptor tyrosine kinase (RTK) family that is classified as a putative pseudokinase. RYK regulates fundamental biological processes including cell differentiation, migration and target selection, axon outgrowth and pathfinding by transducing signals across the plasma...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3776778?pdf=render |
| _version_ | 1818198417739874304 |
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| author | Michael M Halford Maria L Macheda Clare L Parish Elena A Takano Stephen Fox Daniel Layton Edouard Nice Steven A Stacker |
| author_facet | Michael M Halford Maria L Macheda Clare L Parish Elena A Takano Stephen Fox Daniel Layton Edouard Nice Steven A Stacker |
| author_sort | Michael M Halford |
| collection | DOAJ |
| description | RYK is an unusual member of the receptor tyrosine kinase (RTK) family that is classified as a putative pseudokinase. RYK regulates fundamental biological processes including cell differentiation, migration and target selection, axon outgrowth and pathfinding by transducing signals across the plasma membrane in response to the high affinity binding of Wnt family ligands to its extracellular Wnt inhibitory factor (WIF) domain. Here we report the generation and initial characterization of a fully human inhibitory monoclonal antibody to the human RYK WIF domain. From a naïve human single chain fragment variable (scFv) phage display library, we identified anti-RYK WIF domain-specific scFvs then screened for those that could compete with Wnt3a for binding. Production of a fully human IgG1κ from an inhibitory scFv yielded a monoclonal antibody that inhibits Wnt5a-responsive RYK function in a neurite outgrowth assay. This antibody will have immediate applications for modulating RYK function in a range of settings including development and adult homeostasis, with significant potential for therapeutic use in human pathologies. |
| first_indexed | 2024-12-12T02:05:33Z |
| format | Article |
| id | doaj.art-ea185b217d6047a2890c848bb18c3f44 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T02:05:33Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ea185b217d6047a2890c848bb18c3f442022-12-22T00:42:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7544710.1371/journal.pone.0075447A fully human inhibitory monoclonal antibody to the Wnt receptor RYK.Michael M HalfordMaria L MachedaClare L ParishElena A TakanoStephen FoxDaniel LaytonEdouard NiceSteven A StackerRYK is an unusual member of the receptor tyrosine kinase (RTK) family that is classified as a putative pseudokinase. RYK regulates fundamental biological processes including cell differentiation, migration and target selection, axon outgrowth and pathfinding by transducing signals across the plasma membrane in response to the high affinity binding of Wnt family ligands to its extracellular Wnt inhibitory factor (WIF) domain. Here we report the generation and initial characterization of a fully human inhibitory monoclonal antibody to the human RYK WIF domain. From a naïve human single chain fragment variable (scFv) phage display library, we identified anti-RYK WIF domain-specific scFvs then screened for those that could compete with Wnt3a for binding. Production of a fully human IgG1κ from an inhibitory scFv yielded a monoclonal antibody that inhibits Wnt5a-responsive RYK function in a neurite outgrowth assay. This antibody will have immediate applications for modulating RYK function in a range of settings including development and adult homeostasis, with significant potential for therapeutic use in human pathologies.http://europepmc.org/articles/PMC3776778?pdf=render |
| spellingShingle | Michael M Halford Maria L Macheda Clare L Parish Elena A Takano Stephen Fox Daniel Layton Edouard Nice Steven A Stacker A fully human inhibitory monoclonal antibody to the Wnt receptor RYK. PLoS ONE |
| title | A fully human inhibitory monoclonal antibody to the Wnt receptor RYK. |
| title_full | A fully human inhibitory monoclonal antibody to the Wnt receptor RYK. |
| title_fullStr | A fully human inhibitory monoclonal antibody to the Wnt receptor RYK. |
| title_full_unstemmed | A fully human inhibitory monoclonal antibody to the Wnt receptor RYK. |
| title_short | A fully human inhibitory monoclonal antibody to the Wnt receptor RYK. |
| title_sort | fully human inhibitory monoclonal antibody to the wnt receptor ryk |
| url | http://europepmc.org/articles/PMC3776778?pdf=render |
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