Integrin-linked kinase regulates p38 MAPK-dependent cell cycle arrest in ureteric bud development.
The integrin-linked kinase (ILK), pinch and parvin ternary complex connects the cytoplasmic tails of beta1 integrins to the actin cytoskeleton. We recently showed that constitutive expression of ILK and alpha parvin in both the ureteric bud and the metanephric mesenchyme of the kidney is required for kidney development. In this study, we define the selective role of ILK in the ureteric bud of the mouse kidney in renal development by deleting it in the ureteric cell lineage before the onset of branching morphogenesis (E10.5). Although deleting ILK resulted in only a moderate decrease in branching, the mice died at 8 weeks of age from obstruction due to the unprecedented finding of intraluminal collecting duct cellular proliferation. ILK deletion in the ureteric bud resulted in the inability of collecting duct cells to undergo contact inhibition and to activate p38 mitogen-activated protein kinase (MAPK) in vivo and in vitro. p38 MAPK activation was not dependent on the kinase activity of ILK. Thus, we conclude that ILK plays a crucial role in activating p38 MAPK, which regulates cell cycle arrest of epithelial cells in renal tubulogenesis.
Smeeton
Joanna
J
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Zhang
Xi
X
Bulus
Nada
N
Mernaugh
Glenda
G
Lange
Anika
A
Karner
Courtney M
CM
Carroll
Thomas J
TJ
Fässler
Reinhard
R
Pozzi
Ambra
A
Rosenblum
Norman D
ND
Zent
Roy
R
D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014513:Ureter / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099200:Scaffold Protein ILK
D018398:Homeodomain Proteins; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000099200:Scaffold Protein ILK; C093253:Hoxb7 protein, mouse
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