title: Deorphanization of the human leukocyte tyrosine kinase (LTK) receptor by a signaling screen of the extracellular proteome.
abstract: There are many transmembrane receptor-like proteins whose ligands have not been identified. A strategy for finding ligands when little is known about their tissue source is to screen each extracellular protein individually expressed in an array format by using a sensitive functional readout. Taking this approach, we have screened a large collection (3,191 proteins) of extracellular proteins for their ability to activate signaling of an orphan receptor, leukocyte tyrosine kinase (LTK). Only two related secreted factors, FAM150A and FAM150B (family with sequence similarity 150 member A and member B), stimulated LTK phosphorylation. FAM150A binds LTK extracellular domain with high affinity (K(D) = 28 pM). FAM150A stimulates LTK phosphorylation in a ligand-dependent manner. This strategy provides an efficient approach for identifying functional ligands for other orphan receptors.
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Lily I
authors.initials: LI
authors.lastname: Pao
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Aileen
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Brace
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Robert
authors.initials: R
authors.lastname: Halenbeck
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Hsu
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Bray
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hestir
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bosch
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Ernestine
authors.initials: E
authors.lastname: Lee
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Haixia
authors.initials: H
authors.lastname: Liu
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Wong
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080.
authors.forename: W Michael
authors.initials: WM
authors.lastname: Kavanaugh
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, CA 94080 rusty.williams@fiveprime.com.
authors.forename: Lewis T
authors.initials: LT
authors.lastname: Williams
mesh_terms: D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C000609778:ALKAL1 protein, human; C000609777:ALKAL2 protein, human; D016207:Cytokines; D020543:Proteome; C489300:LTK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: FAM150A; extracellular protein; leukocyte tyrosine kinase; library screening; orphan receptor