کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815190 | 1058457 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Phosphodiesterase 4 interacts with the 5-HT4(b) receptor to regulate cAMP signaling
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کلمات کلیدی
IBMXPDE4D5PDE4D3AKAPGRKPDE3BHEK293pKa5-hydroxytryptaminePDE5-HTDMSO - DMSOG protein-coupled receptor kinase - G پروتئین گیرنده کینازisobutylmethylxanthine - ایزوبویل methylxanthineImmunoprecipitation - تخریب ایمنیDimethyl sulfoxide - دیمتیل سولفواکسیدhuman embryonic kidney cell line - سلول انسانی جنین انسانPhosphodiesterase - فسفو دی استرازA-kinase anchoring protein - پروتئین anchoring A-kinaseprotein kinase A - پروتئین کیناز A
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Phosphodiesterase 4 interacts with the 5-HT4(b) receptor to regulate cAMP signaling Phosphodiesterase 4 interacts with the 5-HT4(b) receptor to regulate cAMP signaling](/preview/png/10815190.png)
چکیده انگلیسی
Phosphodiesterase (PDE) 3 and PDE4, which degrade cyclic adenosine monophosphate (cAMP), are important regulators of 5-hydroxytryptamine (5-HT) 4 receptor signaling in cardiac tissue. Therefore, we investigated whether they interact with the 5-HT4(b) receptor, and whether A-kinase anchoring proteins (AKAPs), scaffolding proteins that bind to the regulatory subunit of protein kinase A (PKA) and contribute to the spacial-temporal control of cAMP signaling, are involved in the regulation of 5-HT4(b) receptor signaling. By measuring PKA activity in the absence and presence of PDE3 and PDE4 inhibitiors, we found that constitutive signaling of the overexpressed HA-tagged 5-HT4(b) receptor in HEK293 cells is regulated predominantly by PDE4, with a secondary role for PDE3 that is unmasked in the presence of PDE4 inhibition. Overexpressed PDE4D3 and PDE3A1, and to a smaller extent PDE4D5 co-immunoprecipitate constitutively with the 5-HT4(b) receptor. PDE activity measurements in immunoprecipitates of the 5-HT4(b) receptor confirm the association of PDE4D3 with the receptor and provide evidence that the activity of this PDE may be increased upon receptor stimulation with 5-HT. A possible involvement of AKAPs in 5-HT4(b) receptor signaling was uncovered in experiments using the St-Ht31 inhibitor peptide, which disrupts the interaction of AKAPs with PKA. However, St-Ht31 did not influence 5-HT4(b) receptor-stimulated PKA activity, and endogenous AKAP79 and gravin were not found in immunoprecipitates of the 5-HT4(b) receptor. In conclusion, we found that both PDE3A1 and PDE4D3 are integrated into complexes that contain the 5-HT4(b) receptor and may thereby regulate 5-HT4(b) receptor-mediated signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 26, Issue 11, November 2014, Pages 2573-2582
Journal: Cellular Signalling - Volume 26, Issue 11, November 2014, Pages 2573-2582
نویسندگان
S. Weninger, K. Van Craenenbroeck, R.T. Cameron, F. Vandeput, M.A. Movsesian, G.S. Baillie, R.A. Lefebvre,