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Differential regula...
Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the beta(3)-adrenergic receptor agonist CL316243: effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes
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- Ahmad, Faiyaz (författare)
- NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA
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- Lindh, Rebecka (författare)
- Lund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups,Lund University, Department Expt Med Science, S-22184 Lund, Sweden
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- Tang, Yan (författare)
- NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA
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- Ruishalme, Iida (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Öst, Anita (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Sahachartsiri, Bobby (författare)
- NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA
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- Strålfors, Peter (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Degerman, Eva (författare)
- Lund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups,Lund University, Department Expt Med Science, S-22184 Lund, Sweden
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- C Manganiello, Vincent (författare)
- NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA
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(creator_code:org_t)
- 2009
- 2009
- Engelska.
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Ingår i: BIOCHEMICAL JOURNAL. - 0264-6021. ; 424:3, s. 399-410
- Relaterad länk:
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- In adipocytes, PDE3B (phosphodiesterase 3B) is an important regulatory effector in signalling pathways controlled by insulin and cAMP-increasing hormones. Stimulation of 3T3-L1 adipocytes with insulin or the beta(3)-adrenergic receptor agonist CL316243 (termed CL) indicated that insulin preferentially phosphorylated/activated PDE3B associated with internal membranes (endoplasmic reticulum/Golgi), whereas CL preferentially phosphorylated/activated PDE3B associated with caveolae. siRNA (small interfering RNA)-mediated KD (knockdown) of CAV-1 (caveolin-1) in 3T3-L1 adipocytes resulted in down-regulation of expression of membrane-associated PDE3B. Insulin-induced activation of PDE3B was reduced, whereas CL-mediated activation was almost totally abolished. Similar results were obtained in adipocytes from Cav-1-deficient mice. siRNA-mediated KID of CAV-1 in 3T3-L1 adipocytes also resulted in inhibition of CL-stimulated phosphorylation of HSL (hormone-sensitive lipase) and perilipin A, and of lipolysis. Superose 6 gel-filtration chromatography of solubilized membrane proteins from adipocytes stimulated with insulin or CL demonstrated the reversible assembly of distinct macromolecular complexes that contained P-32-phosphorylated PDE3B and signalling molecules thought to be involved in its activation. Insulin- and CL-induced macromolecular complexes were enriched in cholesterol, and contained certain common signalling proteins [14-3-3, PP2A (protein phosphatase 2A) and cav-1]. The complexes present in insulin-stimulated cells contained tyrosine-phosphorylated IRS-1 (insulin receptor substrate 1) and its downstream signalling proteins, whereas CL-activated complexes contained beta(3)-adrenergic receptor, PKA-RII [PKA (cAMP-dependent protein kinase)-regulatory subunit] and HSL. Insulin- and CL-mediated macromolecular complex formation was significantly inhibited by CAV-1 KID. These results suggest that cav-1 acts as a molecular chaperone or scaffolding molecule in cholesterol-rich lipid rafts that may be necessary for the proper stabilization and activation of PDE3B in response to CL and insulin.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- adipocyte
- beta(3)-adrenergic receptor
- caveolin-1
- insulin
- protein kinase A (PKA)
- phosphodiesterase 3 (PDE3)
- MEDICINE
- MEDICIN
- kinase A (PKA)
- protein
- insulin
- caveolin-1
- adipocyte
- beta(3)-adrenergic receptor
- phosphodiesterase 3 (PDE3)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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