Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the TSH receptor and Galpha(s), which activate the cAMP cascade in the thyroid gland have been much studied, nothing is known about the adenylyl cyclase (AC) isoforms which are actually involved in this pathway. To characterize the cAMP generation in the dog and human thyroid gland, resulting from the presence of distinct adenylyl cyclase families, the responses to various agents (Ca2+, calmodulin (CaM), phorbol esters (TPA) and thapsigargin (Tg)) were studied. These experiments suggest a role of at least two families of cyclases: cyclases negatively modulated by Ca2+ (ACV or ACVI) and cyclases positively modulated by PKC (ACII, ACIII or ACVII). To further analyze by other experimental procedures the expression pattern of the cyclase isoforms in the thyroid gland, Northern blotting, Western blotting and RT-PCR experiments were performed. The results clearly suggest that in both species, three different adenylyl cyclases ACIII, ACVI and ACIX are mainly expressed in thyrocytes.
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PMID:Expression of multiple adenylyl cyclase isoforms in human and dog thyroid. 1116 2

Adenylyl cyclase (AC) superactivation is thought to play an important role in opioid tolerance, dependence, and withdrawal. In the present study, we investigated the involvement of protein kinases in chronic delta-opioid agonist-mediated AC superactivation in Chinese hamster ovary (CHO) cells stably expressing the human delta-opioid receptor (hDOR/CHO). Maximal forskolin-stimulated cAMP formation in hDOR/CHO cells increased by 472 +/- 91, 399 +/- 2, and 433 +/- 73% after chronic treatment with the delta-opioid agonists (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxy-benzyl]-N,N-diethyl benzamide (SNC 80), [d-Pen2,d-Pen5]-enkephalin, and deltorphin II, respectively. Concurrently, chronic SNC 80 (1 micro M, 4-h) treatment augmented 32P incorporation into a 200-kDa protein immunoreactive with the ACV/VI antibody by 300 +/- 60% in hDOR/CHO cell lysates. The calmodulin antagonist calmidazolium significantly attenuated chronic deltorphin II-mediated AC superactivation. Tyrosine kinase (genistein) and protein kinase C (chelerythrine) inhibitors individually had minimal effect on chronic delta-opioid agonist-mediated AC superactivation. Conversely, simultaneous treatment with both genistein and chelerythrine significantly attenuated AC superactivation. Because we showed previously that the Raf-1 inhibitor 3-(3,5-dibromo-4-hydroxybenzylidene-5-iodo-1,3-dihydro-indol-2-one (GW5074) attenuates AC superactivation, we hypothesize that parallel calmidazolium-, chelerythrine-, and genistein-sensitive pathways converge at Raf-1 to mediate AC superactivation by phosphorylating AC VI in hDOR/CHO cells.
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PMID:Converging protein kinase pathways mediate adenylyl cyclase superactivation upon chronic delta-opioid agonist treatment. 1266 Mar 10