Adenylyl cyclase 6 is selectively regulated by protein kinase A in a region involved in G alpha(s) stimulation.
Item
-
Title
-
Adenylyl cyclase 6 is selectively regulated by protein kinase A in a region involved in G alpha(s) stimulation.
-
Identifier
-
AAI9830693
-
identifier
-
9830693
-
Creator
-
Chen, Yibang.
-
Contributor
-
Adviser: Ravi Iyengar
-
Date
-
1998
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Biology, Molecular | Health Sciences, Pharmacology | Biology, Cell | Biology, Animal Physiology
-
Abstract
-
Transmembrane signaling through the receptor-G{dollar}\rm\sb{lcub}s{rcub}{dollar}-adenylyl cyclase complex has been studied for a long time as a model for signal transduction through heterotrimeric G proteins. Agonists bind to receptors triggering activation of G{dollar}\rm\alpha\sb{lcub}s{rcub}{dollar}, activated G{dollar}\rm\alpha\sb{lcub}s{rcub}{dollar} then stimulates adenylyl cyclases to increase intracellular cAMP. As a second messenger, cAMP is involved in many downstream biological activities through the activation of protein kinase A. Previous studies have shown that in certain cell types that express adenylyl cyclase 6 (AC6), heterologous desensitization includes reduction of the capability of adenylyl cyclases to be stimulated. In my thesis I have studied the effect of Protein Kinase A on adenylyl cyclases. Protein Kinase A treatment of recombinant adenylyl cyclase 6 in insect cell membranes results in a selective loss of stimulation by high ({dollar}>{dollar}10nM) concentrations of G{dollar}\rm\alpha\sb{lcub}s{rcub}{dollar}. Similar treatment of AC1 or AC2 did not affect G{dollar}\rm\alpha\sb{lcub}s{rcub}{dollar} stimulation. Conversion of Ser-674 in AC6 to an Ala blocks protein kinase A phosphorylation and Protein Kinase A mediated inhibition of G{dollar}\rm\alpha\sb{lcub}s{rcub}{dollar} stimulation. A peptide FLLT encoding the region 660-682 of AC6 blocks stimulation of AC6 and AC2 by high concentrations of G{dollar}\rm\alpha\sb{lcub}s{rcub}{dollar}. Substitution of Ser-674 to Asp in the peptide renders the peptide ineffective, indicating that the region 660-682 of AC6 is involved in regulation of signal transfer from G{dollar}\rm\alpha\sb{lcub}s{rcub}{dollar}. This region contains a conserved motif present in most adenylyl cyclases, however the Protein Kinase A phosphorylation site is unique to members of the AC6 family. These observations suggest a mechanism of how isoform selective regulatory diversity can be obtained within conserved regions involved in signal communication.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
