title: clr-1 encodes a receptor tyrosine phosphatase that negatively regulates an FGF receptor signaling pathway in Caenorhabditis elegans.
abstract: Receptor tyrosine phosphatases have been implicated in playing important roles in cell signaling events by their ability to regulate the level of protein tyrosine phosphorylation. Although the catalytic activity of their phosphatase domains has been well established, the biological roles of these molecules are, for the most part, not well understood. Here we show that the Caenorhabditis elegans protein CLR-1 (CLeaR) is a receptor tyrosine phosphatase (RTP) with a complex extracellular region and two intracellular phosphatase domains. Mutations in clr-1 result in a dramatic Clr phenotype that we have used to study the physiological requirements for the CLR-1 RTP. We show that the phosphatase activity of the membrane-proximal domain is essential for the in vivo function of CLR-1. By contrast, we present evidence that the membrane-distal domain is not required to prevent the Clr phenotype in vivo. The Clr phenotype of clr-1 mutants is mimicked by activation of the EGL-15 fibroblast growth factor receptor (FGFR) and is suppressed by mutations that reduce or eliminate the activity of egl-15. Our data strongly indicate that CLR-1 attenuates the action of an FGFR-mediated signaling pathway by dephosphorylation.
authors.affiliation: Yale University School of Medicine, Department of Genetics, New Haven, Connecticut 06520-8005, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kokel
authors.forename: C Z
authors.initials: CZ
authors.lastname: Borland
authors.forename: L
authors.initials: L
authors.lastname: DeLong
authors.forename: H R
authors.initials: HR
authors.lastname: Horvitz
authors.forename: M J
authors.initials: MJ
authors.lastname: Stern
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D018244:Chromosomes, Artificial, Yeast; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000235:genetics; D018509:DNA, Helminth / Q000235:genetics; D004926:Escherichia coli; D017238:Genes, Helminth; D016153:Genes, Suppressor; D018740:Genetic Heterogeneity; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010641:Phenotype; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D054557:Receptor-Like Protein Tyrosine Phosphatases; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D013696:Temperature; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D018509:DNA, Helminth; C112493:EGL-15 protein, C elegans; D015801:Helminth Proteins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C112492:CLR-1 protein, C elegans; D017027:Protein Tyrosine Phosphatases; D054557:Receptor-Like Protein Tyrosine Phosphatases