腺苷酸环化酶
G蛋白
Gsα亚单位
cAMP依赖途径
细胞生物学
生物
阿德西6
异三聚体G蛋白
蛋白激酶A
阿德西9
阿德西10
G蛋白偶联受体激酶
β肾上腺素能受体激酶
信号转导
阿德西3
MAPK/ERK通路
G蛋白偶联受体
百日咳毒素
磷酸化
阿片受体
蛋白磷酸酶2
作者
Sumita Chakrabarti,Annette Regec,Alan R. Gintzler
标识
DOI:10.1016/j.molbrainres.2005.04.004
摘要
Abstract Chronic morphine augments protein kinase C (PKC) phosphorylation of G β , which enhances the potency of G βγ to stimulate adenylyl cyclase II (ACII) activity. The present study demonstrates an in vivo association between phosphorylated G β and a specific PKC isoform, PKCγ. We investigated the association of G β and PKCγ by assessing the ability of anti-PKCγ antibodies to co-immunoprecipitate G β from 32 P-radiolabeled Chinese Hamster Ovary cells stably transfected with a μ-opioid receptor (MOR-CHO). PKCγ immunoprecipitate (IP) obtained from MOR-CHO membranes contained radiolabeled signals of ≈33 and 36–38 kDa that were subsequently identified as G β (s). Chronic morphine significantly increased (≈75%) the magnitude of 32 P incorporated into G β present in PKCγ IP. This suggests that G β is an in vivo substrate for PKCγ, which mediates the chronic morphine-induced increment in G β phosphorylation. In order to evaluate AC as a putative effector for phosphorylated G βγ , its presence in IP obtained using anti-AC antibodies was evaluated. Autoradiographic analyses of AC IP also revealed the presence of phosphorylated G β (s), the magnitude of which was significantly enhanced (≈60%) following chronic morphine treatment. This indicates that phosphorylated G βγ associates and presumably interacts in vivo with AC, indicating that it is a target for the enhanced phosphorylated G βγ that is generated following chronic morphine treatment. This would contribute to the previously observed shift from predominantly G iα inhibitory to G βγ stimulatory AC signaling following chronic morphine. The PKCγ–G β –AC complex identified in this study provides an organizational framework for understanding the well-documented participation of PKCγ in opioid tolerance-producing mechanisms.
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