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

Smeeton J, Zhang X, Bulus N, Mernaugh G, Lange A, Karner CM, Carroll TJ, Fässler R, Pozzi A, Rosenblum ND, Zent R
Development. 2010 137 (19): 3233-43

PMID: 20823064 · PMCID: PMC2934735 · DOI:10.1242/dev.052845

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.

MeSH Terms (16)

Animals Cell Adhesion Cell Cycle Cell Movement Cell Proliferation Cells, Cultured Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic Homeodomain Proteins Mice Mice, Inbred C57BL Mice, Knockout p38 Mitogen-Activated Protein Kinases Protein-Serine-Threonine Kinases Signal Transduction Ureter

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