title: Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development.
abstract: The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that clp24 knockdown in Danio rerio and Xenopus laevis results in defective lymphatic development. Targeted disruption of Clp24 in mice led to enlarged lymphatic vessels having an abnormal smooth muscle cell coating. We also show that the Clp24(-/-) phenotype was further aggravated in the Vegfr2(+/LacZ) or Vegfr3(+/LacZ) backgrounds and that CLP24 interacts with vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3 and attenuates the transcription factor CREB phosphorylation via these receptors. Our results indicate that CLP24 is a novel regulator of VEGFR-2 and VEGFR-3 signaling pathways and of normal lymphatic vessel structure.
authors.affiliation: Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland.
authors.forename: Pipsa
authors.initials: P
authors.lastname: Saharinen
authors.forename: Hanna
authors.initials: H
authors.lastname: Helotera
authors.forename: Juho
authors.initials: J
authors.lastname: Miettinen
authors.forename: Camilla
authors.initials: C
authors.lastname: Norrmen
authors.forename: Gabriela
authors.initials: G
authors.lastname: D'Amico
authors.forename: Michael
authors.initials: M
authors.lastname: Jeltsch
authors.forename: Tobias
authors.initials: T
authors.lastname: Langenberg
authors.forename: Wouter
authors.initials: W
authors.lastname: Vandevelde
authors.forename: Annelii
authors.initials: A
authors.lastname: Ny
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D042601:Lymphatic Vessels / Q000196:embryology* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000166:cytology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3