Ureteric bud outgrowth in response to RET activation is mediated by phosphatidylinositol 3-kinase

Ming Jer Tang, Yi Cai, Si Jie Tsai, Yang Kao Wang, Gregory R. Dressler

研究成果: Article同行評審

121 引文 斯高帕斯(Scopus)


The c-ret gene encodes a receptor tyrosine kinase (RET) essential for the development of the kidney and enteric nervous system. Activation of RET requires the secreted neurotrophin GDNF (glial cell line-derived neurotrophic factor) and its high affinity receptor, a glycosyl phosphatidylinositol-linked cell surface protein GFRα1. In the developing kidney, RET, GDNF, and GFRα1 are all required for directed outgrowth and branching morphogenesis of the ureteric bud epithelium. Using MDCK renal epithelial cells as a model system, activation of RET induces cell migration, scattering, and formation of filopodia and lamellipodia. RET-expressing MDCK cells are able to migrate toward a focalized source of GDNF. In this report, the intracellular signaling mechanisms regulating RET-dependent migration and chemotaxis are examined. Activation of RET resulted in increased levels of phosphatidylinositol 3-kinase (PI3K) activity and Akt/PKB phosphorylation. This increase in PI3K activity is essential for regulating the GDNF response, since the specific inhibitor, LY294002, blocks migration and chemotaxis of MDCK cells. Using an in vitro organ culture assay, inhibition of PI3K completely blocks the GDNF-dependent outgrowth of ectopic ureter buds. PI3K is also essential for branching morphogenesis once the ureteric bud has invaded the kidney mesenchyme. The data suggest that activation of RET in the ureteric bud epithelium signals through PI3K to control outgrowth and branching morphogenesis.

頁(從 - 到)128-136
期刊Developmental Biology
出版狀態Published - 2002 3月 1

All Science Journal Classification (ASJC) codes

  • 分子生物學
  • 發展生物學
  • 細胞生物學


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