Abstract:
:Phosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule recruited to the membrane by activated growth factor receptors. The p85 subunit of PI 3-kinase links the catalytic p110 subunit to activated growth factor receptors and is required for enzymatic activity of p110. In this report, we describe the effects of expressing novel forms of p110 that are targeted to the membrane by either N-terminal myristoylation or C-terminal farnesylation. The expression of membrane-localized p110 is sufficient to trigger downstream responses characteristic of growth factor action, including the stimulation of pp70 S6 kinase, Akt/Rac, and Jun N-terminal kinase (JNK). These responses can also be triggered by expression of a form of p110 (p110*) that is cytosolic but exhibits a high specific activity. Finally, targeting of pl10* to the membrane results in maximal activation of downstream responses. Our data demonstrate that either membrane-targeted forms of p110 or a form of p110 with high specific activity can act as constitutively active PI 3-kinases and induce PI 3-kinase-dependent responses in the absence of growth factor stimulation. The results also show that PI 3-kinase activation is sufficient to stimulate several kinases that appear to function in different signaling pathways.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Klippel A,Reinhard C,Kavanaugh WM,Apell G,Escobedo MA,Williams LTdoi
10.1128/mcb.16.8.4117subject
Has Abstractpub_date
1996-08-01 00:00:00pages
4117-27issue
8eissn
0270-7306issn
1098-5549journal_volume
16pub_type
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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:1988-04-01 00:00:00
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doi:10.1128/mcb.14.1.116
更新日期:1994-01-01 00:00:00
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更新日期:1998-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.9.4788
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