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PI3K signaling in the regulation of branching morphogenesis
Authors:Zhu Wenting  Nelson Celeste M
Affiliation:Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Abstract:Branching morphogenesis drives the formation of epithelial organs including the mammary gland, lung, kidney, salivary gland and prostate. Branching at the cellular level also drives development of the nervous and vascular systems. A variety of signaling pathways are orchestrated together to establish the pattern of these branched organs. The phosphoinositide 3-kinase (PI3K) signaling network is of particular interest because of the diverse outcomes it generates, including proliferation, motility, growth, survival and cell death. Here, we focus on the role of the PI3K pathway in the development of branched tissues. Cultured cells, explants and transgenic mice have revealed that the PI3K pathway is critical for the regulation of cell proliferation, apoptosis and motility during branching of tissues.
Keywords:BAD, Bcl-2-associated death promoter   ECM, extracellular matrix   EGF, epidermal growth factor   FGF, fibroblast growth factor   GDNF, glial cell line-derived neurotrophic factor   GPCR, G protein-coupled receptor   HGF, hepatocyte growth factor   MAPK, mitogen-activated protein kinase   MM, metanephric mesenchyme   MMP, matrix metalloproteinase   MMTV, mouse mammary tumor virus   mTOR, mammalian target of rapamycin   NRG1, neuregulin-1   PAK, p21-activated kinase   PDK1, phosphoinositide-dependent protein kinase-1   PH, pleckstrin homology   PI3K, phosphoinositide 3-kinase   PIKE, phosphoinositide 3-kinase enhancer   PIP2, phosphatidylinositol-4,5-bisphosphate   PIP3, phosphatidylinositol-3,4,5-trisphosphate   PKB, protein kinase B   PTEN, phosphatase and tensin homology deleted on chromosome ten   RTK, receptor tyrosine kinase   SMG, submandibular gland   SP, surfactant protein   TEB, terminal end bud   TGF, transforming growth factor   UB, ureteric bud   UGS, urogenital sinus   UPS, ubiquitin proteasome system   VEGF, vascular endothelial growth factor   WD, Wolffian duct
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