The WIF module

Abstract

The Ryk (for related-to-tyrosine-kinase) receptor tyrosine kinases form a distinct subfamily of tyrosine kinases. They have an unusually short extracellular region 1 Hovens C.M. et al. Ryk, a receptor tyrosine kinase-related molecule with unusual kinase domain motifs. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 11818-11822 Crossref PubMed Scopus (114) Google Scholar and unique substitutions in their catalytic domains 1 Hovens C.M. et al. Ryk, a receptor tyrosine kinase-related molecule with unusual kinase domain motifs. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 11818-11822 Crossref PubMed Scopus (114) Google Scholar , 2 Stacker S.A. et al. Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK). Oncogene. 1993; 8: 1347-1356 PubMed Google Scholar , 3 Tamagnone L. et al. The human ryk cDNA sequence predicts a protein containing two putative transmembrane segments and a tyrosine kinase catalytic domain. Oncogene. 1993; 8: 2009-2014 PubMed Google Scholar , 4 Dura J.M. et al. The Drosophila learning and memory gene linotte encodes a putative receptor tyrosine kinase homologous to the human RYK gene product. FEBS Lett. 1995; 370: 250-254 Abstract Full Text PDF PubMed Scopus (58) Google Scholar , 5 Oates A.C. et al. Embryonic expression and activity of doughnut, a second RYK homolog in Drosophila. Mech. Dev. 1998; 78: 165-169 Crossref PubMed Scopus (17) Google Scholar , 6 Halford M.M. et al. Genomic structure and expression of the mouse growth factor receptor related to tyrosine kinases (Ryk)s. J. Biol. Chem. 1999; 274: 7379-7390 Crossref PubMed Scopus (19) Google Scholar . The phylogenetic conservation of Ryk proteins from Caenorhabditis elegans and Drosophila to mammals strongly argues for an important and basic function of these proteins. Studies on mutants of the Drosophila derailed (drl) gene have shown that this Ryk protein plays a crucial role in cell-recognition processes controlling nervous system development and muscle development 4 Dura J.M. et al. The Drosophila learning and memory gene linotte encodes a putative receptor tyrosine kinase homologous to the human RYK gene product. FEBS Lett. 1995; 370: 250-254 Abstract Full Text PDF PubMed Scopus (58) Google Scholar . linotte (lio) mutants of the drl gene present structural brain defects in the adult central complex and mushroom bodies, indicating that this receptor tyrosine kinase is required for neuronal pathway selection 7 Moreau-Fauvarque C. et al. The receptor tyrosine kinase gene linotte is required for neuronal pathway selection in the Drosophila mushroom bodies. Mech. Dev. 1998; 78: 47-61 Crossref PubMed Scopus (56) Google Scholar , 8 Simon A.F. et al. The Drosophila putative kinase linotte (derailed) prevents central brain axons from converging on a newly described interhemispheric ring. Mech. Dev. 1998; 76: 45-55 Crossref PubMed Scopus (52) Google Scholar . Derailed mutants of the drl gene are defective in insertion of somatic muscles into the epidermis, suggesting that the mechanism for selecting sites for muscle attachment is biochemically similar to that used in axon pathfinding 9 Callahan C.A. et al. derailed is required for muscle attachment site selection in Drosophila. Development. 1996; 122: 2761-2767 PubMed Google Scholar . DNT, a second Ryk homologue in Drosophila, encoded by doughnut, is capable of a partial rescue of the muscle attachment defect of drl−/− embryos, suggesting that DNT and DRL proteins have overlapping biochemical activities 5 Oates A.C. et al. Embryonic expression and activity of doughnut, a second RYK homolog in Drosophila. Mech. Dev. 1998; 78: 165-169 Crossref PubMed Scopus (17) Google Scholar . The Ryk-homologue of C. elegans (gene C18B6.1) corresponds to the lin-18 gene that is required for cell–cuticle recognition 10 Serfas M.S. Tyner A.L. Ryk is expressed in a differentiation-specific manner in epithelial tissues and is strongly induced in decidualizing uterine stroma. Oncogene. 1998; 17: 3435-3444 Crossref PubMed Scopus (14) Google Scholar , 11 Ferguson E.L. et al. A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. Nature. 1987; 326: 259-267 Crossref PubMed Scopus (255) Google Scholar . Mammalian Ryk proteins are found in most tissues but little is known about their function 11 Ferguson E.L. et al. A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. Nature. 1987; 326: 259-267 Crossref PubMed Scopus (255) Google Scholar . Murine Ryk protein is induced in epithelial cells seeking a final place in a differentiated tissue, or during remodelling of the endometrium 10 Serfas M.S. Tyner A.L. Ryk is expressed in a differentiation-specific manner in epithelial tissues and is strongly induced in decidualizing uterine stroma. Oncogene. 1998; 17: 3435-3444 Crossref PubMed Scopus (14) Google Scholar , which suggests that mammalian Ryk proteins might also be involved in cellular recognition processes.