Protein kinase C stimulates adenylate cyclase activity in prolactin-secreting rat adenoma (GH4C1) pituicytes by inactivating the inhibitory GTP-binding protein Gi.
Protein kinase C stimulates adenylate cyclase activity in prolactin-secreting rat adenoma (GH4C1) pituicytes by inactivating the inhibitory GTP-binding protein Gi.
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蛋白激酶 C 通过灭活抑制性 GTP 结合蛋白 Gi，刺激分泌催乳素的大鼠腺瘤 (GH4C1) 垂体细胞中的腺苷酸环化酶活性。
DOI：
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Kaare M. Gautvik
中科院分区：
文献类型：
--
作者：
J. Gordeladze;Trine Bjøro;Peter A. Torjesen;B. C. Ostberg;Egil Haug;Kaare M. Gautvik
佛波酯12-O-十四烷酰基-佛波13-乙酸酯（TPA）和促甲状腺激素释放激素对大鼠垂体腺瘤GH4 C1垂体细胞催乳素的释放和合成有相加的刺激作用。TPA和促甲状腺激素都能激活破裂细胞膜中的腺苷酸环化酶。当结合时，促分泌素显示累加效应。TPA没有改变激素、鸟苷5 '-[β，γ-亚氨基]三磷酸或毛喉素激活腺苷酸环化酶的时间进程（时滞），也没有影响酶对游离Mg 2+的表观亲和力（基础，7.2 mM;甲状腺释放素增强，2.2 mM）。TPA介导的腺苷酸环化酶激活完全依赖于外源性添加的鸟苷三磷酸。ED 50（产生半数最大激活的剂量）为60 μ M。获得游离Ca 2+是表达TPA激活酶所必需的，然而，钙调蛋白的存在不是强制性的。TPA刺激的腺苷酸环化酶活性被生物学上无活性的佛波酯、4 α-佛波二癸酸酯、蛋白激酶C抑制剂多粘菌素B和百日咳毒素所消除，而甲状腺释放素敏感的腺苷酸环化酶保持不受影响。实验条件下，已知的蛋白激酶C转移到质膜，而不诱导腺苷酸环化酶脱敏，增加了基础和促甲状腺激素刺激的酶的活性，而绝对TPA增强腺苷酸环化酶保持。从S49细胞周期小鼠淋巴瘤细胞与GH4 C1细胞膜中提取的GTP结合抑制蛋白Gi的结合产生了基础和抑制剂刺激的腺苷酸环化酶活性的降低，而生长抑素环化酶的净抑制显著增强。然而，TPA完全恢复的基础和腺苷酸环化酶引起的活动，在Gi丰富的膜。最后，TPA完全取消生长抑素诱导的抑制腺苷酸环化酶在杂交和非杂交膜。这些数据表明，在GH4 C1细胞中，蛋白激酶C刺激佛波醇酯完全失活的抑制性GTP结合蛋白的n α 1亚基，留下的n β亚基功能完整。还可以推断，促甲状腺激素通过激活刺激性GTP结合蛋白Gs来传递其对腺苷酸环化酶的主要作用。
The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and thyroliberin exerted additive stimulatory effects on prolactin release and synthesis in rat adenoma GH4C1 pituicytes in culture. Both TPA and thyroliberin activated the adenylate cyclase in broken cell membranes. When combined, the secretagogues displayed additive effects. TPA did not alter the time course (time lag) of adenylate cyclase activation by hormones, guanosine 5'-[beta,gamma-imino]triphosphate or forskolin, nor did it affect the enzyme's apparent affinity (basal, 7.2 mM; thyroliberin-enhanced, 2.2 mM) for free Mg2+. The TPA-mediated adenylate cyclase activation was entirely dependent on exogenously added guanosine triphosphate. ED50 (dose yielding half-maximal activation) was 60 microM. Access to free Ca2+ was necessary to express TPA activation of the enzyme, however, the presence of calmodulin was not mandatory. TPA-stimulated adenylate cyclase activity was abolished by the biologically inactive phorbol ester, 4 alpha-phorbol didecanoate, by the protein kinase C inhibitor polymyxin B and by pertussis toxin, while thyroliberin-sensitive adenylate cyclase remained unaffected. Experimental conditions known to translocate protein kinase C to the plasma membrane and without inducing adenylate cyclase desensitization, increased both basal and thyroliberin-stimulated enzyme activities, while absolute TPA-enhanced adenylate cyclase was maintained. Association of extracted GTP-binding inhibitory protein, Gi, from S49 cyc- murine lymphoma cells with GH4C1 cell membranes yielded a reduction of basal and hormone-stimulated adenylate cyclase activities, while net inhibition of the cyclase of somatostatin was dramatically enhanced. However, TPA restored completely basal and hormone-elicited adenylate cyclase activities in the Gi-enriched membranes. Finally, TPA completely abolished the somatostatin-induced inhibition of adenylate cyclase in both hybrid and non-hybrid membranes. These data suggest that, in GH4C1 cells, protein kinase C stimulation by phorbol esters completely inactivates the n alpha i subunit of the inhibitory GTP-binding protein, leaving the n beta subunit functionally intact. It can also be inferred that thyroliberin conveys its main effect on the adenylate cyclase through activation of the stimulatory GTP-binding protein, Gs.
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腺苷酸环化酶的抑制性鸟嘌呤核苷酸结合调节成分。
DOI：
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发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Katada,T;Bokoch,GM;Northup,JK;Ui,M;Gilman,AG
通讯作者：
Gilman,AG
促甲状腺激素释放激素诱导 GH4C1 大鼠垂体细胞中蛋白激酶 C 的重新分布。
DOI：
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发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fearon,CW;TashjianJr,AH
通讯作者：
TashjianJr,AH
DOI：
10.1073/pnas.83.5.1184
发表时间：
1986-03-01
影响因子：
11.1
作者：
GANONG, BR;LOOMIS, CR;BELL, RM
通讯作者：
BELL, RM
钙和二酰甘油作为促甲状腺素释放激素作用中双重第二信使作用的证据：Ca 2 的参与。
影响因子：
4.8
作者：
Martin,TF;Kowalchyk,JA
通讯作者：
Kowalchyk,JA
佛波酯对胞质游离 Ca2+ 浓度的双重作用以及用离子霉素重建急性促甲状腺素释放激素反应。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Albert,PR;TashjianJr,AH
通讯作者：
TashjianJr,AH