title: Function of the Ryk intracellular domain in C. elegans vulval development.
abstract: BACKGROUND
  Ryk is a subfamily of receptor tyrosine kinases, which along with Frizzled and Ror, function as Wnt receptors. Vertebrate Ryk intracellular domain (ICD) is released from the cell membrane by a proteolytic cleavage in the transmembrane region and localizes to the nucleus. In C. elegans, Ryk is encoded by the lin-18 gene and regulates the polarity of the P7.p vulval cell.
  
  
  RESULTS
  Based on Western blots, we were unable to detect the presence of the cleaved LIN-18 ICD fragment. Functional assays found that LIN-18 intracellular domain is not absolutely required for LIN-18 function, consistent with previous results. However, overexpression of the LIN-18 intracellular domain fragment (LIN-18ICD) weakly enhanced the phenotype of lin-18 loss-of-function mutants. Furthermore, this activity was specific to the serine-rich juxtamembrane region. We also found that the nuclear localization of LIN-18ICD fragment can be regulated by Wnt pathway components including CAM-1/Ror, and by PAR-5/14-3-3.
  
  
  CONCLUSIONS
  Release of LIN-18ICD by cleavage at the membrane is not the main mechanism of LIN-18 signaling in vulval cells. However, our results suggest that LIN-18 intracellular domain interacts with Wnt pathway components and a 14-3-3 protein and likely plays a minor role in LIN-18 signaling.
authors: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Woon Cheng
authors: WC
authors: Poh
authors: Yanqing
authors: Y
authors: Shen
authors: Takao
authors: T
authors: Inoue
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D014844:Vulva / Q000196:embryology* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C492691:LIN-18 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases
keywords: cell polarity; nuclear localization; signal transduction; vulval development