%0 Journal Article %1 Schulz1996 %A Schulz, K. %A Danner, S. %A Bauer, P. %A Schroder, S. %A Lohse, M. J. %D 1996 %J J Biol Chem %K & 1-Methyl-3-isobutylxanthine/pharmacology AMP-Dependent AMP/metabolism Acid Adenylate Adrenergic Amino Blotting, Cell Cyclase/metabolism Cyclic Data Eye GTP-Binding Humans Inhibitors/pharmacology Isoproterenol/pharmacology Kinases/antagonists Line Molecular Phosphodiesterase Phosphoproteins/*biosynthesis Protein Proteins/*biosynthesis Regulators Sequence Signal Transduction Transfection Western beta-Agonists/pharmacology beta/metabolism inhibitors Receptor Proteins/metabolism %N 37 %P 22546-51 %T Expression of phosducin in a phosducin-negative cell line reveals functions of a Gbetagamma-binding protein %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8798422 %V 271 %X Phosducin is a member of the large group of proteins that bind to G-protein betagamma-subunits (Gbetagamma) and whose biological functions are often unknown. Human A431 cells do not contain detectable amounts of phosducin. We generated A431 cells expressing phosducin at a level of approximately 1 pmol/mg of cytosolic protein, which is approximately 10% of the phosducin level in brain. cAMP accumulation in response to beta2-adrenergic receptor agonists was enhanced at early times in phosducin-expressing cells, but reached a lower plateau than in control cells. Permeabilization of the cells with digitonin did not change this pattern, but allowed the introduction of specific inhibitors: antibodies to phosducin abolished all differences between the two cell lines. Inhibitors of the beta-adrenergic receptor kinase abolished the differences at early time points. An almost complete loss of beta2-adrenergic receptor desensitization in the phosducin-expressing cells was also observed when intact cells were desensitized and receptor function was then determined in membrane preparations. Inhibition of protein kinase A accentuated the effects of phosducin, suggesting that also in vivo phosducin is regulated by this kinase. These data indicate that phosducin affects G-protein-mediated signaling in at least two ways: it dampens the overall responsiveness, and it impairs the rapid desensitization mediated by the beta-adrenergic receptor kinase.

@article{Schulz1996, abstract = {Phosducin is a member of the large group of proteins that bind to G-protein betagamma-subunits (Gbetagamma) and whose biological functions are often unknown. Human A431 cells do not contain detectable amounts of phosducin. We generated A431 cells expressing phosducin at a level of approximately 1 pmol/mg of cytosolic protein, which is approximately 10% of the phosducin level in brain. cAMP accumulation in response to beta2-adrenergic receptor agonists was enhanced at early times in phosducin-expressing cells, but reached a lower plateau than in control cells. Permeabilization of the cells with digitonin did not change this pattern, but allowed the introduction of specific inhibitors: antibodies to phosducin abolished all differences between the two cell lines. Inhibitors of the beta-adrenergic receptor kinase abolished the differences at early time points. An almost complete loss of beta2-adrenergic receptor desensitization in the phosducin-expressing cells was also observed when intact cells were desensitized and receptor function was then determined in membrane preparations. Inhibition of protein kinase A accentuated the effects of phosducin, suggesting that also in vivo phosducin is regulated by this kinase. These data indicate that phosducin affects G-protein-mediated signaling in at least two ways: it dampens the overall responsiveness, and it impairs the rapid desensitization mediated by the beta-adrenergic receptor kinase.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Schulz, K. and Danner, S. and Bauer, P. and Schroder, S. and Lohse, M. J.}, biburl = {https://www.bibsonomy.org/bibtex/24042eee7755a39659daf4ce6c0e2482a/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {ac968bcbd8b5d103d80603c1909abe10}, intrahash = {4042eee7755a39659daf4ce6c0e2482a}, issn = {0021-9258 (Print) 0021-9258 (Linking)}, journal = {J Biol Chem}, keywords = {& 1-Methyl-3-isobutylxanthine/pharmacology AMP-Dependent AMP/metabolism Acid Adenylate Adrenergic Amino Blotting, Cell Cyclase/metabolism Cyclic Data Eye GTP-Binding Humans Inhibitors/pharmacology Isoproterenol/pharmacology Kinases/antagonists Line Molecular Phosphodiesterase Phosphoproteins/*biosynthesis Protein Proteins/*biosynthesis Regulators Sequence Signal Transduction Transfection Western beta-Agonists/pharmacology beta/metabolism inhibitors Receptor Proteins/metabolism}, month = {Sep 13}, note = {Schulz, K Danner, S Bauer, P Schroder, S Lohse, M J Research Support, Non-U.S. Gov't United states The Journal of biological chemistry J Biol Chem. 1996 Sep 13;271(37):22546-51.}, number = 37, pages = {22546-51}, shorttitle = {Expression of phosducin in a phosducin-negative cell line reveals functions of a Gbetagamma-binding protein}, timestamp = {2010-12-14T18:22:42.000+0100}, title = {Expression of phosducin in a phosducin-negative cell line reveals functions of a Gbetagamma-binding protein}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8798422}, volume = 271, year = 1996 }