Identification of RanBP 9/10 as Interacting Partners for Protein Kinase C (PKC) γ/δ and the D₁Dopamine 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) ␦-and PKC␥-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 PKC␥ and PKC␦. Both RanBP9 and RanBP10 were found to specifically coimmunoprecipitate with both PKC␥ and PKC␦; 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

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

“…PKCα has been linked to increased risk for hemorrhagic transformation following ischemic stroke [69]. PKCδ contributes to a release of reactive oxygen species and apoptosis following ischemia [70, 71]. PKCδ likewise contributes to increased BBB permeability via activation of matrix metalloproteinase-9 and phosphorylation of occludin [72, 73].…”

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

“…Alternately spliced variants, the D2S and D2L dopamine receptors, display different levels of sensitivity to desensitization by PKC depending on the relative location of their phosphorylation and pseudosubstrate sites (Liu et al, 1992;Morris et al, 2007). Dopamine D1 receptors can also be phosphorylated and regulated by PKC␥ and PKC␦ as well as their interacting proteins, RanBP9 and RanBP10, in an ethanol-dependent manner, indicating a new mechanism for the potentiation of dopaminergic neurotransmission by ethanol (Rex et al, 2008;Rex et al, 2010).…”

PKA and ERK1/2 are involved in dopamine D1 receptor-induced heterologous desensitization of the δ opioid receptor

“…Activation of the D 1 R has been shown to activate PKA, PKC and extracellular signal-regulated kinase 1/2 (ERK1/2) (Flores-Hernandez et al, 2000; Chao et al, 2002a; Chao et al, 2002b; Zhang et al, 2004; Mangiavacchi and Wolf, 2004; Chen et al, 2004b; Hopf et al, 2005; Rex et al, 2010; Rankin and Sibley, 2010). To examine if these kinases are involved in D 1 R-induced desensitization of the DOPR, CHO-FLAG-DOPR/HA-D 1 R cells were pretreated for 20 min with vehicle, the PKA inhibitor Rp-cAMP-SH (10 μM), the PKC inhibitor GF 109203X (10 μM), the PI3K inhibitor wortmannin (100 nM) or the MEK1 inhibitor PD98059 (10 μM), and then incubated with vehicle or SKF-82958 (10 μM) for 30 min in the presence of the phosphatase inhibitor calyculin A (10 nM).…”