title: Btk29A promotes Wnt4 signaling in the niche to terminate germ cell proliferation in Drosophila.
abstract: Btk29A is the Drosophila ortholog of the mammalian Bruton's tyrosine kinase (Btk), mutations of which in humans cause a heritable immunodeficiency disease. Btk29A mutations stabilized the proliferating cystoblast fate, leading to an ovarian tumor. This phenotype was rescued by overexpression of wild-type Btk29A and phenocopied by the interference of Wnt4-β-catenin signaling or its putative downstream nuclear protein Piwi in somatic escort cells. Btk29A and mammalian Btk directly phosphorylated tyrosine residues of β-catenin, leading to the up-regulation of its transcriptional activity. Thus, we identify a transcriptional switch involving the kinase Btk29A/Btk and its phosphorylation target, β-catenin, which functions downstream of Wnt4 in escort cells to terminate Drosophila germ cell proliferation through up-regulation of piwi expression. This signaling mechanism likely represents a versatile developmental switch.
authors.affiliation: Department of Developmental Biology and Neurosciences, Tohoku University Graduate School of Life Sciences, Sendai 980-8577, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hamada-Kawaguchi
authors.forename: Beston F
authors.initials: BF
authors.lastname: Nore
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kuwada
authors.forename: C I Edvard
authors.initials: CI
authors.lastname: Smith
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000096:biosynthesis*; D049109:Cell Proliferation; D053903:DNA Breaks, Double-Stranded; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055785:Gene Knockdown Techniques; D042822:Genomic Instability; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D034741:RNA, Small Interfering; D051153:Wnt Proteins; C454442:Wnt4 protein, Drosophila; D051176:beta Catenin; C116498:piwi protein, Drosophila; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C474449:Btk29A protein, Drosophila