title: Identification of RanBP 9/10 as interacting partners for protein kinase C (PKC) gamma/delta and the D1 dopamine receptor: regulation of PKC-mediated receptor phosphorylation.
abstract: We reported previously that ethanol treatment regulates D(1) receptor phosphorylation and signaling in a protein kinase C (PKC) delta- and PKCgamma-dependent fashion by a mechanism that may involve PKC isozyme-specific interacting proteins. Using a PKC isozyme-specific coimmunoprecipitation approach coupled to mass spectrometry, we report the identification of RanBP9 and RanBP10 as novel interacting proteins for both PKCgamma and PKCdelta. Both RanBP9 and RanBP10 were found to specifically coimmunoprecipitate with both PKCgamma and PKCdelta; however, this association did not seem to mediate the ethanol regulation of the PKCs. It is noteworthy that the D(1) receptor was also found to specifically coimmunoprecipitate with RanBP9/10 from human embryonic kidney (HEK) 293T cells and with endogenous RanBP9 from rat kidney. RanBP9 and RanBP10 were also found to colocalize at the cellular level with the D(1) receptor in both kidney and brain tissue. Although overexpression of RanBP9 or RanBP10 in HEK293T cells did not seem to alter the kinase activities of either PKCdelta or PKCgamma, both RanBP proteins regulated D(1) receptor phosphorylation, signaling, and, in the case of RanBP9, expression. Specifically, overexpression of either RanBP9 or RanBP10 enhanced basal D(1) receptor phosphorylation, which was associated with attenuation of D(1) receptor-stimulated cAMP accumulation. Moreover, treatment of cells with select PKC inhibitors blocked the RanBP9/10-dependent increase in basal receptor phosphorylation, suggesting that phosphorylation of the receptor by PKC is regulated by RanBP9/10. These data support the idea that RanBP9 and RanBP10 may function as signaling integrators and dictate the efficient regulation of D(1) receptor signaling by PKCdelta and PKCgamma.
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Rex
authors.forename: Michele L
authors.initials: ML
authors.lastname: Rankin
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Lu
authors.forename: Charles R
authors.initials: CR
authors.lastname: Gerfen
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.forename: David R
authors.initials: DR
authors.lastname: Sibley
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C529801:RANBP10 protein, human; C116005:Ran binding protein 9; D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; C087857:protein kinase C gamma; D011493:Protein Kinase C; D051745:Protein Kinase C-delta
references.citation: Biochem Biophys Res Commun. 2004 Jan 9;313(2):320-6
references.pmid: 14684163
references.citation: J Biol Chem. 1999 Mar 26;274(13):8886-92
references.pmid: 10085132
references.citation: J Biol Chem. 1999 Sep 17;274(38):27039-46
references.pmid: 10480917
references.citation: Eur J Pharmacol. 1998 Jul 24;353(2-3):149-58
references.pmid: 9726645
references.citation: Mol Pharmacol. 1999 Oct;56(4):675-83
references.pmid: 10496949
references.citation: J Biol Chem. 1993 Mar 25;268(9):6090-6
references.pmid: 8454583
references.citation: Neuropsychopharmacology. 2008 Nov;33(12):2900-11
references.pmid: 18288091
references.citation: PLoS Genet. 2008 Feb;4(2):e26
references.pmid: 18266473
references.citation: Eur J Pharmacol. 1992 Dec 15;229(2-3):203-9
references.pmid: 1362704
references.citation: J Neurosci. 2007 Sep 12;27(37):9817-23
references.pmid: 17855595
references.citation: Pharmacol Biochem Behav. 2003 Sep;76(2):335-42
references.pmid: 14592686
references.citation: Mol Pharmacol. 2003 Jan;63(1):9-18
references.pmid: 12488531
references.citation: Brain Res. 1994 Nov 7;663(1):140-4
references.pmid: 7850462
references.citation: J Biol Chem. 2002 Jun 14;277(24):22073-84
references.pmid: 11934885
references.citation: Development. 1999 May;126(10):2033-44
references.pmid: 10207129
references.citation: J Biol Chem. 1996 Feb 16;271(7):3771-8
references.pmid: 8631993
references.citation: J Biol Chem. 1997 Nov 14;272(46):29200-6
references.pmid: 9360998
references.citation: J Biol Chem. 2001 Aug 10;276(32):29644-50
references.pmid: 11387319
references.citation: J Biol Chem. 2007 Jul 20;282(29):21285-300
references.pmid: 17395585
references.citation: Mol Pharmacol. 2001 Feb;59(2):310-21
references.pmid: 11160868
references.citation: J Neuroimmune Pharmacol. 2007 Sep;2(3):290-5
references.pmid: 18040864
references.citation: J Neurochem. 2003 Oct;87(2):395-406
references.pmid: 14511117
references.citation: FEBS Lett. 2008 Jul 9;582(16):2453-7
references.pmid: 18555800
references.citation: Kidney Int. 2006 Sep;70(6):1072-9
references.pmid: 16850019
references.citation: J Biol Chem. 2008 Dec 26;283(52):36441-53
references.pmid: 18984584
references.citation: J Biol Chem. 2004 Mar 26;279(13):13027-34
references.pmid: 14722085
references.citation: Neuron. 2008 Jun 12;58(5):736-48
references.pmid: 18549785
references.citation: Immunogenetics. 2009 Mar;61(3):163-76
references.pmid: 19238338
references.citation: Mol Pharmacol. 2002 Apr;61(4):806-16
references.pmid: 11901220
references.citation: Eur Neuropsychopharmacol. 2009 Jun;19(6):440-50
references.pmid: 19268547
references.citation: J Neurochem. 2008 Jun 1;105(6):2237-48
references.pmid: 18298663
references.citation: J Biol Chem. 1993 May 5;268(13):9194-7
references.pmid: 8486620
references.citation: Biochemistry. 1999 Oct 19;38(42):13787-94
references.pmid: 10529223
references.citation: J Biol Chem. 1997 Dec 19;272(51):32019-24
references.pmid: 9405395
references.citation: FEBS Lett. 2004 Jan 2;556(1-3):276-80
references.pmid: 14706863
references.citation: J Biol Chem. 2008 May 16;283(20):14109-19
references.pmid: 18347012
references.citation: Mol Pharmacol. 1996 Oct;50(4):966-76
references.pmid: 8863843
references.citation: Neurosci Lett. 2009 Dec 11;466(3):154-8
references.pmid: 19788913
references.citation: Nat Cell Biol. 2001 May;3(5):492-8
references.pmid: 11331877
references.citation: Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H551-69
references.pmid: 18083900
references.citation: Annu Rev Neurosci. 2004;27:107-44
references.pmid: 15217328
references.citation: Mol Pharmacol. 2006 Mar;69(3):759-69
references.pmid: 16338988
references.citation: J Biol Chem. 2003 Oct 3;278(40):38970-9
references.pmid: 12857743
references.citation: Physiol Rev. 1998 Jan;78(1):189-225
references.pmid: 9457173
references.citation: Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):839-43
references.pmid: 8302854
references.citation: Alcohol Clin Exp Res. 2004 Nov;28(11):1666-75
references.pmid: 15547453