Abstract:
:Using cultured airway smooth muscle cells, we showed previously that the platelet-derived growth factor (PDGF) receptor uses the G-protein, G(i), to stimulate Grb-2-associated phosphoinositide 3-kinase (PI3K) activity. We also showed that this was an intermediate step in the activation of p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) by PDGF. We now present two lines of evidence that provide further support for this model. First, we report that PDGF stimulates the G(i)-mediated tyrosine phosphorylation of the Grb-2 adaptor protein, Gab1. This phosphorylation appears to be necessary for association of PI3K1a with the Gab1-Grb-2 complex. Second, PI3K appears to promote the subsequent association of dynamin II (which is involved in clathrin-mediated endocytic processing) with the complex. Furthermore, inhibitors of PI3K and clathrin-mediated endocytosis reduced the PDGF-dependent activation of p42/p44 MAPK, suggesting a role for PI3K in the endocytic signaling process leading to stimulation of p42/p44 MAPK. Together, these results begin to define a common signaling model for certain growth factor receptors (e.g., PDGF, insulin, insulin-like growth factor-1, and fibroblast growth factor) which use G(i) to transmit signals to p42/p44 MAPK.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Rakhit S,Pyne S,Pyne NJdoi
10.1124/mol.58.2.413keywords:
subject
Has Abstractpub_date
2000-08-01 00:00:00pages
413-20issue
2eissn
0026-895Xissn
1521-0111journal_volume
58pub_type
杂志文章abstract::Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in dopamine (DA), 1-methyl-4-phenylpyridium (MPP(+)) transport, and cocaine analog binding. In a previous study, the functional analyses on the chimeras of human and bovine DAT have revealed that the region from residues 133 throu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-03-01 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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更新日期:2000-09-01 00:00:00