Abstract:
:Strong evidence indicates that endosome-localized epidermal growth factor receptor (EGFR) plays an important role in cell signaling. However, elimination of endosomal signaling does not attenuate EGF-induced physiological outcomes, arguing against physiological relevance. Recently we established a system to specifically activate endosome-associated EGFR in the absence of any plasma membrane activation of EGFR and showed that endosomal EGFR signaling is sufficient to support cell survival. However, this pure endosomal signaling of EGFR does not stimulate cell proliferation, because EGFR only remained activated for less than 2 h following its stimulation at endosomes, while DNA synthesis generally requires growth factor exposure for 8 h or more. Here we report that the prolonged requirement for EGF to stimulate epithelial cell proliferation can be substituted for with two short pulses of EGF. By combining the two short pulses of EGF stimulation with our previously established method to generate endosomal EGFR signaling, we are able to generate two pulses of endosomal EGFR signaling. In this way, we demonstrated that two pulses of endosomal EGFR signaling are sufficient to stimulate cell proliferation. The first pulse of EGFR signaling induces exit from quiescence into G(1) phase and appears to render cells responsive to subsequent mitogenic stimulus. This second pulse, required several hours later, drives cells through the restriction point of late G(1) and into S phase. We further showed that the two pulses of endosomal EGFR signaling engaged cell cycle machinery the same way as the two pulses of standard EGFR signaling. Moreover, two pulses of endosomal EGFR signaling stimulated downstream signaling cascades in a similar way to the two pulses of standard EGFR activation. The data therefore demonstrate that signals transduced from internalized EGFR, with or without a contribution from the plasma membrane, fully satisfy the physiological requirements for S-phase entry.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Pennock S,Wang Zdoi
10.1128/mcb.23.16.5803-5815.2003subject
Has Abstractpub_date
2003-08-01 00:00:00pages
5803-15issue
16eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::DNA mismatch repair maintains genomic stability by detecting and correcting mispaired DNA sequences and by signaling cell death when DNA repair fails. The mechanism by which mismatch repair coordinates DNA damage and repair with cell survival or death is not understood, but it suggests the need for regulation. Since t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.9.3320-3328.2003
更新日期:2003-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.2.1059
更新日期:1993-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.1.82
更新日期:1983-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.2.887
更新日期:1987-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.10.6.2909
更新日期:1990-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.9.7.2890
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pub_type: 杂志文章
doi:10.1128/mcb.12.10.4412
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.5.1489-1497.2003
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pub_type: 杂志文章
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更新日期:1990-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.2.6.653
更新日期:1982-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.6.2104
更新日期:1987-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/MCB.01558-09
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.4.2040
更新日期:1991-04-01 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:2000-06-01 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:2006-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00087-09
更新日期:2009-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.5.2832
更新日期:1991-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.4.1642
更新日期:1989-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.14.11.7153
更新日期:1994-11-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/mcb.16.9.5015
更新日期:1996-09-01 00:00:00
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更新日期:2009-07-01 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:1984-07-01 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:1996-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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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:2011-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1982-01-01 00:00:00