The novel protein kinase Vlk is essential for stromal function of mesenchymal cells.
From a list of protein kinases (PKs) that are newly induced upon differentiation of mouse embryonic stem cells to mesendoderm, we identified a previously uncharacterized kinase, Vlk (vertebrate lonesome kinase), that is well conserved in vertebrates but has no homologs outside of the vertebrate lineage. Its kinase domain cannot be classified into any of the previously defined kinase groups or families. Although Vlk is first expressed in E-cadherin-positive anterior visceral endoderm and mesendoderm, its expression is later confined to E-cadherin-negative mesenchyme. Vlk is enriched in the Golgi apparatus and blocks VSVG transport from the Golgi to the plasma membrane. Targeted disruption of Vlk leads to a defect in lung development and to delayed ossification of endochondral bone. Vlk(-/-) mice display neonatal lethality due to respiratory failure, with a suckling defect arising from a cleft palate. Our results demonstrate that Vlk is a novel vertebrate-specific PK that is involved in the regulation of the rate of protein export from the Golgi, thereby playing an important role in the formation of functional stroma by mesenchymal cells.
Kinoshita
Masaki
M
Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan. mask@cdb.riken.jp
Era
Takumi
T
Jakt
Lars Martin
LM
Nishikawa
Shin-Ichi
S
D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000196:embryology; D015820:Cadherins / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002972:Cleft Palate / Q000196:embryology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism; D008168:Lung / Q000002:abnormalities / Q000196:embryology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology
D015820:Cadherins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C543966:Vlk protein, mouse