Ser/ Thr residues at α3/β5 loop of Gαs are important in morphine‐induced adenylyl cyclase sensitization but not mitogen‐activated protein kinase phosphorylation

The signaling switch of β2‐adrenergic and μ1‐opioid receptors from stimulatory G‐protein (Gαs) to inhibitory G‐protein (Gαi) (and vice versa) influences adenylyl cyclase (AC) and extracellular‐regulated kinase (ERK)1/2 activation. Post‐translational modifications, including dephosphorylation of Gαs,...

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Bibliographic Details
Published in:The FEBS journal 2012-02, Vol.279 (4), p.650-660
Main Authors: Seyedabadi, Mohammad, Ostad, Seyed Nasser, Albert, Paul R., Dehpour, Ahmad R., Rahimian, Reza, Ghazi‐Khansari, Mahmoud, Ghahremani, Mohammad H.
Format: Article
Language:English
Subjects:
Adenylyl Cyclase Inhibitors
Adenylyl Cyclases - metabolism
adrenergic
Adrenergic beta-Agonists - pharmacology
Analgesics, Opioid - pharmacology
Animals
Blotting, Western
Cell Line, Tumor
Cyclic AMP - metabolism
Enzyme Activation - drug effects
GTP-Binding Protein alpha Subunits, Gs - genetics
GTP-Binding Protein alpha Subunits, Gs - metabolism
Gαs
Immunoprecipitation
Isoproterenol - pharmacology
MAPK
Mice
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Mitogen-Activated Protein Kinases - metabolism
Morphine - pharmacology
Mutation
opioid
Phosphorylation - drug effects
Protein Binding - drug effects
Receptors, Adrenergic, beta-2 - metabolism
Receptors, Opioid, mu - metabolism
Serine - genetics
Serine - metabolism
signaling switch
Threonine - genetics
Threonine - metabolism
Transfection
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Summary:The signaling switch of β2‐adrenergic and μ1‐opioid receptors from stimulatory G‐protein (Gαs) to inhibitory G‐protein (Gαi) (and vice versa) influences adenylyl cyclase (AC) and extracellular‐regulated kinase (ERK)1/2 activation. Post‐translational modifications, including dephosphorylation of Gαs, enhance opioid receptor coupling to Gαs. In the present study, we substituted the Ser/Thr residues of Gαs at the α3/β5 and α4/β6 loops aiming to study the role of Gαs lacking Ser/Thr phosphorylation with respect to AC sensitization and mitogen‐activated protein kinase activation. Isoproterenol increased the cAMP concentration (EC50 = 22.8 ± 3.4 μm) in Gαs‐transfected S49 cyc− cells but not in nontransfected cells. However, there was no significant difference between the Gαs‐wild‐type (wt) and mutants. Morphine (10 μm) inhibited AC activity more efficiently in cyc− compared to Gαs‐wt introduced cells (P 
ISSN:1742-464X
1742-4658
DOI:10.1111/j.1742-4658.2011.08459.x