Integrin-linked kinase regulates p38 MAPK-dependent cell cycle arrest in ureteric bud development.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Smeeton, J; Zhang, X; Bulus, N; Mernaugh, G; Lange, A; Karner, CM; Carroll, TJ; Fässler, R; Pozzi, A; Rosenblum, ND; Zent, R

Published Date

  • October 2010

Published In

Volume / Issue

  • 137 / 19

Start / End Page

  • 3233 - 3243

PubMed ID

  • 20823064

Pubmed Central ID

  • 20823064

Electronic International Standard Serial Number (EISSN)

  • 1477-9129

International Standard Serial Number (ISSN)

  • 0950-1991

Digital Object Identifier (DOI)

  • 10.1242/dev.052845

Language

  • eng