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:
Journal of neurobiology
影响因子:
--
通讯作者:
Epstein,ML
Epstein,ML
中科院分区:
--
文献类型:
--
作者:
Focke,PJ;Schiltz,CA;Jones,SE;Watters,JJ;Epstein,ML

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肠神经系统(ENS)由神经嵴细胞进入肠道、迁移、增殖并分化为神经元和胶质细胞发育而成。生长因子胶质源性神经营养因子(GDNF)刺激肠嵴源性细胞的增殖和存活。我们研究了GDNF激活的细胞内信号通路及其在增殖中的作用。我们发现,在免疫亲和纯化的胚胎禽肠嵴源细胞培养中,GDNF刺激PI 3激酶下游底物Akt和MAP激酶底物ERK的磷酸化。选择性PI 3激酶抑制剂LY - 294002阻断GDNF刺激纯化的冠细胞中Akt磷酸化,并减少分离鹌鹑肠培养物的增殖。ERK激酶(MEK)抑制剂PD 98059和UO126不减少GDNF刺激的增殖,尽管PD 98059阻断GDNF刺激的ERK磷酸化。我们得出结论,PI 3激酶途径对于GDNF刺激的肠内神经母细胞增殖是必要的。©2001 John Wiley & Sons, Inc中国生物医学工程杂志[J] .中国生物医学工程杂志
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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