Abstract:
:Ras proteins can activate at least three classes of downstream target proteins: Raf kinases, phosphatidylinositol-3 phosphate (PI3) kinase, and Ral-specific guanine nucleotide exchange factors (Ral-GEFs). In NIH 3T3 cells, activated Ral-GEFs contribute to Ras-induced cell proliferation and oncogenic transformation by complementing the activities of Raf and PI3 kinases. In PC12 cells, activated Raf and PI3 kinases mediate Ras-induced cell cycle arrest and differentiation into a neuronal phenotype. Here, we show that in PC12 cells, Ral-GEF activity acts opposite to other Ras effectors. Elevation of Ral-GEF activity induced by transfection of a mutant Ras protein that preferentially activates Ral-GEFs, or by transfection of the catalytic domain of the Ral-GEF Rgr, suppressed cell cycle arrest and neurite outgrowth induced by nerve growth factor (NGF) treatment. In addition, Rgr reduced neurite outgrowth induced by a mutant Ras protein that preferentially activates Raf kinases. Furthermore, inhibition of Ral-GEF activity by expression of a dominant negative Ral mutant accelerated cell cycle arrest and enhanced neurite outgrowth in response to NGF treatment. Ral-GEF activity may function, at least in part, through inhibition of the Rho family GTPases, CDC42 and Rac. In contrast to Ras, which was activated for hours by NGF treatment, Ral was activated for only approximately 20 min. These findings suggest that one function of Ral-GEF signaling induced by NGF is to delay the onset of cell cycle arrest and neurite outgrowth induced by other Ras effectors. They also demonstrate that Ras has the potential to promote both antidifferentiation and prodifferentiation signaling pathways through activation of distinct effector proteins. Thus, in some cell types the ratio of activities among Ras effectors and their temporal regulation may be important determinants for cell fate decisions between proliferation and differentiation.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Goi T,Rusanescu G,Urano T,Feig LAdoi
10.1128/mcb.19.3.1731subject
Has Abstractpub_date
1999-03-01 00:00:00pages
1731-41issue
3eissn
0270-7306issn
1098-5549journal_volume
19pub_type
杂志文章abstract::Placental development initially occurs in a low-oxygen (O2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), HIF1alpha and HIF2alpha, are essential for determining murine placental cell fates. HIF is a heterodimer composed of HIFalpha and HIFbeta (ARNT) subunits. Placentas from...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.23.10479-10491.2005
更新日期:2005-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.11.4335-4348.2005
更新日期:2005-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.23.8809-8819.2003
更新日期:2003-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2006-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.16.5974-5985.2000
更新日期:2000-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.12.6982
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00699-08
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pub_type: 杂志文章
doi:10.1128/MCB.26.2.480-488.2006
更新日期:2006-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1999-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.9.4961
更新日期:1990-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.309
更新日期:1996-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.3.1123
更新日期:1988-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.15.5156-5168.2001
更新日期:2001-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.8.4282
更新日期:1991-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.11.6866
更新日期:1993-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00648-10
更新日期:2011-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.2547
更新日期:1999-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2003-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1993-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2011-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.5.1830
更新日期:1986-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.21.17.6031-6043.2001
更新日期:2001-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2007-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.2987
更新日期:1996-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.5.2457
更新日期:1995-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00415-06
更新日期:2006-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.10.5770
更新日期:1995-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.1.192-198.2006
更新日期:2006-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.4.1179
更新日期:1986-04-01 00:00:00