Enteric neuroblasts require the phosphatidylinositol 3-kinase pathway for GDNF-stimulated proliferation.
Enteric neuroblasts require the phosphatidylinositol 3-kinase pathway for GDNF-stimulated proliferation.
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肠神经母细胞需要磷脂酰肌醇 3 激酶途径来促进 GDNF 刺激的增殖。
DOI:
10.1002/neu.1037
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发表时间:
2001
期刊:
影响因子:
--
通讯作者:
Epstein,ML
中科院分区:
文献类型:
--
作者:
Focke,PJ;Schiltz,CA;Jones,SE;Watters,JJ;Epstein,ML
The enteric nervous system (ENS) develops from neural crest cells that enter the gut, migrate, proliferate, and differentiate into neurons and glia. The growth factor glial‐derived neurotrophic factor (GDNF) stimulates the proliferation and survival of enteric crest‐derived cells. We investigated the intracellular signaling pathways activated by GDNF and their involvement in proliferation. We found that GDNF stimulates the phosphorylation of both the PI 3‐kinase downstream substrate Akt and the MAP kinase substrate ERK in cultures of immunoaffinity‐purified embryonic avian enteric crest‐derived cells. The selective PI 3‐kinase inhibitor LY‐294002 blocked GDNF‐stimulated Akt phosphorylation in purified crest cells, and reduced proliferation in cultures of dissociated quail gut. The ERK kinase (MEK) inhibitors PD 98059 and UO126 did not reduce GDNF‐stimulated proliferation, although PD 98059 blocked GDNF‐stimulated phosphorylation of ERK. We conclude that the PI 3‐kinase pathway is necessary for the GDNF‐stimulated proliferation of enteric neuroblasts. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 306–317, 2001
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