title: The carbonic anhydrase domain of receptor tyrosine phosphatase beta is a functional ligand for the axonal cell recognition molecule contactin.
abstract: Receptor-type protein tyrosine phosphatase beta (RPTP beta) is expressed in the developing nervous system and contains a carbonic anhydrase (CAH) domain as well as a fibronectin type III repeat in its extracellular domain. Fusion proteins containing these domains were used to search for ligands of RPTP beta. The CAH domain bound specifically to a 140 kDa protein expressed on the surface of neuronal cells. Expression cloning in COS7 cells revealed that this protein is contactin, a GPI membrane-anchored neuronal cell recognition molecule. The CAH domain of RPTP beta induced cell adhesion and neurite growth of primary tectal neurons, and differentiation of neuroblastoma cells. These responses were blocked by antibodies against contactin, demonstrating that contactin is a neuronal receptor for RPTP beta. These experiments show that an individual domain of RPTP beta acts as a functional ligand for the neuronal receptor contactin. The interaction between contactin and RPTP beta may generate unidirectional or bidirectional signals during neural development.
authors.affiliation: SUGEN, Incorporated, Redwood City, California 94063-4720, USA.
authors.forename: E
authors.initials: E
authors.lastname: Peles
authors.forename: M
authors.initials: M
authors.lastname: Nativ
authors.forename: P L
authors.initials: PL
authors.lastname: Campbell
authors.forename: T
authors.initials: T
authors.lastname: Sakurai
authors.forename: R
authors.initials: R
authors.lastname: Martinez
authors.forename: S
authors.initials: S
authors.lastname: Lev
authors.forename: D O
authors.initials: DO
authors.lastname: Clary
authors.forename: J
authors.initials: J
authors.lastname: Schilling
authors.forename: G
authors.initials: G
authors.lastname: Barnea
authors.forename: G D
authors.initials: GD
authors.lastname: Plowman
authors.forename: M
authors.initials: M
authors.lastname: Grumet
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001254:Astrocytoma; D001369:Axons / Q000502:physiology*; D001665:Binding Sites; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D058966:Contactins; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D002256:Carbonic Anhydrases