Linked Life Data

9463474

Source:http://linkedlifedata.com/resource/pubmed/id/9463474

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-3-10
pubmed:abstractText
Forskolin potently activates all cloned mammalian adenylyl cyclases except type IX by interacting with two homologous cytoplasmic domains (C1 and C2) that form the catalytic core. A mutational analysis of the IIC2 protein (C2 domain from type II adenylyl cyclase) and forskolin analogs suggests that Ser942 interacts with the 7-acetyl group of forskolin. The C1/C2 complex has only one forskolin, one ATP, and one binding site for the alpha subunit of the G protein that stimulates adenylyl cyclase (Gsalpha) and its structure may be modeled using the three-dimensional structure of (IIC2/forskolin)2. The Ser942 mutation defines which forskolin in the (IIC2/forskolin)2 structure exists in C1/C2 complex. Thus, the forskolin-binding site is close to the Gsalpha-binding site but distal (15-20A) from the catalytic site. Mutation from Leu912 of IIC2 protein to tyrosine or alanine severely reduces Gsalpha activation and completely prevents forskolin activation. The corresponding residue of Leu912 is Tyr1082 at type IX isoform of adenylyl cyclase. Similar to recombinant type IX enzyme, soluble adenylyl cyclase derived from mouse-type IX adenylyl cyclase is sensitive to Gsalpha activation but not to forskolin. Changing Tyr1082 to leucine makes soluble type IX adenylyl cyclase forskolin-responsive.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
182-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Conversion of forskolin-insensitive to forskolin-sensitive (mouse-type IX) adenylyl cyclase.
pubmed:affiliation
Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, Illinois 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't