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

Joanna Smeeton, Xi Zhang, Nada Bulus, Glenda Mernaugh, Anika Lange, Courtney M. Karner, Thomas J. Carroll, Reinhard Fässler, Ambra Pozzi, Norman D. Rosenblum, Roy Zent

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The integrin-linked kinase (ILK), pinch and parvin ternary complex connects the cytoplasmic tails of β1 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.

Original languageEnglish (US)
Pages (from-to)3233-3243
Number of pages11
JournalDevelopment
Volume137
Issue number19
DOIs
StatePublished - Oct 1 2010

Keywords

  • Branching morphogenesis
  • Growth factor receptors
  • Kidney
  • Mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Integrin-linked kinase regulates p38 MAPK-dependent cell cycle arrest in ureteric bud development'. Together they form a unique fingerprint.

  • Cite this

    Smeeton, J., Zhang, X., Bulus, N., Mernaugh, G., Lange, A., Karner, C. M., Carroll, T. J., Fässler, R., Pozzi, A., Rosenblum, N. D., & Zent, R. (2010). Integrin-linked kinase regulates p38 MAPK-dependent cell cycle arrest in ureteric bud development. Development, 137(19), 3233-3243. https://doi.org/10.1242/dev.052845