Evidence map›Paper›PMID 10449730›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1999

Regions on adenylyl cyclase that are necessary for inhibition of activity by beta gamma and G(ialpha) subunits of heterotrimeric G proteins.

C Wittpoth, K Scholich, Y Yigzaw, T M Stringfield, T B Patel

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 40 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

C WittpothDepartment of Pharmacology, University of Tennessee, The Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA.
K Scholich
Y Yigzaw
T M Stringfield
T B Patel
Vanderbilt University · USUniversity of Tennessee Health Science Center · US

Funding

REGULATION OF A CARDIAC SPECIFIC EFFECTORR01HL059679 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI PATEL, TARUN B · 1998 to 2005
$1.6M
NHLBI NIH HHS HL 59679NHLBI NIH HHS R01 HL059679
6 · The paper itself

Abstract

The two large cytoplasmic domains (C1 and C2) of adenylyl cyclases (AC), when expressed separately and mixed together, reconstitute enzyme activity that can be regulated by various modulators. Therefore, we have used the C1 or its C1a subdomain and C2 regions from type I AC (ACI) and type V AC (ACV) to identify the region on ACI that interacts with beta gamma subunits of heterotrimeric G proteins. In addition, we also used a chimeric C1 domain (VC1aIC1b) in which the C1a region was derived from ACV and the C1b region was from ACI. By mixing the C1 or C1a or VC1aIC1b domains with C2 regions of ACI or ACV, we have shown that the C1a region (amino acids 236-471) of ACI is sufficient to observe beta gamma-mediated inhibition of enzyme activity, which is stimulated by either constitutively active G(salpha) (G(salpha)*) or Ca(2+)/calmodulin (CaM). Although the C1b region and C2 domain of ACI were by themselves not sufficient for inhibition of activity by beta gamma subunits, the presence of both of these regions formed another beta gamma interaction site that was sufficient to observe G(salpha)*- or Ca(2+)/CaM-stimulated activity. Inhibition of AC activity attributable to interaction of beta gamma subunits at either of the two sites was blocked by a peptide (QEHA) that has previously been shown to inhibit the effects of beta gamma on various effectors. Moreover, the C1 region of ACI was sufficient to observe G(ialpha1)-elicited inhibition of Ca(2+)/CaM-stimulated activity. Although the C1a region of ACV was sufficient for inhibition of activity by G(ialpha1), the presence of C1b region from either ACI or ACV increased sensitivity to inhibition by the inhibitory G protein. Thus, the inhibitory influences of G(ialpha1) are mediated on the C1 regions of both ACI and ACV. The effects of beta gamma on ACI can be mediated by interactions with the C1a region and a beta gamma interacting site formed by the C1b and C2 domains of this enzyme.

Indexed as

GTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsHeterotrimeric GTP-Binding ProteinsAdenylyl CyclasesCalmodulinEscherichia coliGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding ProteinsProtein ConformationRecombinant ProteinsStructure-Activity RelationshipAdenylyl CyclasesCalmodulinG-protein Beta gammaGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsGTP-Binding ProteinsHeterotrimeric GTP-Binding ProteinsRecombinant Proteins

Identifiers

PMID10449730
PMCPMC22246
OpenAlexW1489273242

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.