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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Astrocytoma
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Axons / physiology*
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Binding Sites
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Carbonic Anhydrases / chemistry
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Carbonic Anhydrases / metabolism*
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Cell Adhesion Molecules, Neuronal*
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Cell Line
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Chlorocebus aethiops
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Cloning, Molecular
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Contactins
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Humans
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Ligands
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Membrane Proteins / biosynthesis
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Membrane Proteins / metabolism
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Molecular Sequence Data
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / metabolism*
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Neurites / physiology
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Neurons / metabolism
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Protein Binding
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Protein Tyrosine Phosphatases / analysis
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / metabolism*
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Receptor-Like Protein Tyrosine Phosphatases, Class 5
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Tumor Cells, Cultured
Substances
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Cell Adhesion Molecules, Neuronal
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Contactins
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Ligands
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Membrane Proteins
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Nerve Tissue Proteins
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Recombinant Fusion Proteins
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PTPRZ1 protein, human
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Protein Tyrosine Phosphatases
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Receptor-Like Protein Tyrosine Phosphatases, Class 5
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Carbonic Anhydrases