Abstract:
:We reported previously that protein associated with Myc (PAM) interacts with the C2 domain of type V adenylyl cyclase (ACV-C2) and that purified PAM is a potent inhibitor of Galphas-stimulated ACV activity (J Biol Chem 276:47583-47589, 2001). The present study was conducted to identify the region in PAM that inhibits ACV activity and to determine whether its binding with the ACV-C2 is necessary and sufficient to inhibit the enzyme. Coexpression of ACV and full-length PAM or its N-terminal third (PAM-N) in COS-7 cells inhibited isoproterenol-stimulated cAMP accumulation. Deletion of the RCC1 homology domains in PAM-N abolished its ability to inhibit isoproterenol-stimulated cAMP formation in cells. Purified GST fusion protein of the second RCC1 homology domain (RHD2) of PAM was sufficient to bind with ACV-C2 and inhibit Galphas-stimulated ACV activity. In addition, deletion of 11 amino acids in GST-RHD2 obliterated its ability to bind with and inhibit ACV. The C terminus of the RHD2 domain bound with ACV-C2 without inhibiting enzyme activity. Furthermore, substitution of His912 and His913 with alanine in the GST-RHD2 obliterated its ability to inhibit ACV without altering binding to ACV-C2. Likewise, H912/913A mutants of both PAM-N and full-length PAM did not inhibit cAMP formation in cells. Thus, the RHD2 domain of PAM is sufficient to inhibit Galphas-stimulated ACV activity and the binding of RHD2 to ACV-C2 is necessary but not sufficient for this inhibition. Moreover, His912 and His913 in PAM are critical for inhibiting ACV.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Gao X,Patel TBdoi
10.1124/mol.104.005355keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
42-9issue
1eissn
0026-895Xissn
1521-0111pii
mol.104.005355journal_volume
67pub_type
杂志文章abstract::We have found that stypoldione, a bright red o-quinone isolated from the brown alga Stypopodium zonale, inhibits the division of sea urchin embryos in a concentration-dependent manner (IC50 approximately 2.5 X 10(-6) M). Although previous studies have shown this marine natural product to inhibit beef brain microtubule...
journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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更新日期:1986-06-01 00:00:00
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更新日期:2000-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
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journal_title:Molecular pharmacology
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更新日期:1990-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
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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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journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
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doi:
更新日期:2000-05-01 00:00:00
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journal_title:Molecular pharmacology
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doi:
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journal_title:Molecular pharmacology
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更新日期:1994-10-01 00:00:00
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journal_title:Molecular pharmacology
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doi:
更新日期:1989-03-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-08-01 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:1987-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 评论,杂志文章,评审
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更新日期:2006-02-01 00:00:00
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