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Publication : p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation.

First Author  Ventura JJ Year  2007
Journal  Nat Genet Volume  39
Issue  6 Pages  750-8
PubMed ID  17468755 Mgi Jnum  J:122397
Mgi Id  MGI:3714231 Doi  10.1038/ng2037
Citation  Ventura JJ, et al. (2007) p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet 39(6):750-8
abstractText  Stem cell function is central for the maintenance of normal tissue homeostasis. Here we show that deletion of p38alpha mitogen-activated protein (MAP) kinase in adult mice results in increased proliferation and defective differentiation of lung stem and progenitor cells both in vivo and in vitro. We found that p38alpha positively regulates factors such as CCAAT/enhancer-binding protein that are required for lung cell differentiation. In addition, p38alpha controls self-renewal of the lung stem and progenitor cell population by inhibiting proliferation-inducing signals, most notably epidermal growth factor receptor. As a consequence, the inactivation of p38alpha leads to an immature and hyperproliferative lung epithelium that is highly sensitized to K-Ras(G12V)-induced tumorigenesis. Our results indicate that by coordinating proliferation and differentiation signals in lung stem and progenitor cells, p38alpha has a key role in the regulation of lung cell renewal and tumorigenesis.
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