title: Receptor-type protein-tyrosine phosphatase ζ is a functional receptor for interleukin-34.
abstract: Interleukin-34 (IL-34) is highly expressed in brain. IL-34 signaling via its cognate receptor, colony-stimulating factor-1 receptor (CSF-1R), is required for the development of microglia. However, the differential expression of IL-34 and the CSF-1R in brain suggests that IL-34 may signal via an alternate receptor. By IL-34 affinity chromatography of solubilized mouse brain membrane followed by mass spectrometric analysis, we identified receptor-type protein-tyrosine phosphatase ζ (PTP-ζ), a cell surface chondroitin sulfate (CS) proteoglycan, as a novel IL-34 receptor. PTP-ζ is primarily expressed on neural progenitors and glial cells and is highly expressed in human glioblastomas. IL-34 selectively bound PTP-ζ in CSF-1R-deficient U251 human glioblastoma cell lysates and inhibited the proliferation, clonogenicity, and motility of U251 cells in a PTP-ζ-dependent manner. These effects were correlated with an increase in tyrosine phosphorylation of the previously identified PTP-ζ downstream effectors focal adhesion kinase and paxillin. IL-34 binding to U251 cells was abrogated by chondroitinase ABC treatment, and CS competed with IL-34 for binding to the extracellular domain of PTP-ζ and to the cells, indicating a dependence of binding on PTP-ζ CS moieties. This study identifies an alternate receptor for IL-34 that may mediate its action on novel cellular targets.
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Sayan
authors.initials: S
authors.lastname: Nandi
authors.forename: Mario
authors.initials: M
authors.lastname: Cioce
authors.forename: Yee-Guide
authors.initials: YG
authors.lastname: Yeung
authors.forename: Edward
authors.initials: E
authors.lastname: Nieves
authors.forename: Lydia
authors.initials: L
authors.lastname: Tesfa
authors.forename: Haishan
authors.initials: H
authors.lastname: Lin
authors.forename: Amy W
authors.initials: AW
authors.lastname: Hsu
authors.forename: Robert
authors.initials: R
authors.lastname: Halenbeck
authors.forename: Hui-Yong
authors.initials: HY
authors.lastname: Cheng
authors.forename: Solen
authors.initials: S
authors.lastname: Gokhan
authors.forename: Mark F
authors.initials: MF
authors.lastname: Mehler
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D013058:Mass Spectrometry; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D034622:RNA Interference; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: C529076:IL34 protein, human; D007378:Interleukins; D051419:Paxillin; D018123:Receptors, Interleukin; C529075:interleukin-34 receptor, human; D014443:Tyrosine; D016186:Receptor, Macrophage Colony-Stimulating Factor; D051416:Focal Adhesion Protein-Tyrosine Kinases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
keywords: Brain; CSF-1 Receptor; Cell Surface Receptor; Development; Glioblastoma; Interleukin; Neurobiology; Phosphotyrosine Signaling; Signal Transduction; Tyrosine Protein Phosphatase (Tyrosine Phosphatase)