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RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling
Journal article   Peer reviewed

RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling

Seena K. Ajit, Suneela Ramineni, Wade Edris, Rachel A. Hunt, Wah-Tung Hum, John R. Hepler and Kathleen H. Young
Cellular signalling, v 19(4), pp 723-730
2007
DOI: https://doi.org/10.1016/j.cellsig.2006.09.008
PMID: 17126529
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

14-3-3 cAMP Phosphorylation PKCI-1 RGSZ1 Yeast two hybrid
Protein kinase C interacting protein (PKCI-1) was identified among the potential interactors from a yeast two hybrid screen of human brain library using N terminal of RGSZ1 as a bait. The cysteine string region, unique to the RZ subfamily, contributes to the observed interaction because PKCI-1 interacted with N-terminus of RGS17 and GAIP, but not with that of RGS2 or RGS7 where cysteine string motif is absent. The interaction between RGSZ1 and PKCI-1 was confirmed by coimmunoprecipitation and immunofluorescence. PKCI-1 and RGSZ1 could be detected by coimmunoprecipitation using 14-3-3 antibody in cells transfected with PKCI-1 or RGSZ1 respectively, but when transfected with PKCI-1 and RGSZ1 together, only RGSZ1 could be detected. Phosphorylation of Gαz by protein kinase C (PKC) reduces the ability of the RGS to effectively function as GTPase accelerating protein for Gαz, and interferes with ability of Gαz to interact with βγ complex. We investigated the roles of 14-3-3 and PKCI-1 in phosphorylation of Gαz. Phosphorylation of Gαz by PKC was inhibited by 14-3-3 and the presence of PKCI-1 did not provide any further inhibition. PKCI-1 interacts with mu opioid receptor and suppresses receptor desensitization and PKC related mu opioid receptor phosphorylation [W. Guang, H. Wang, T. Su, I.B. Weinstein, J.B. Wang, Mol. Pharmacol. 66 (2004) 1285.]. Previous studies have also shown that mu opioid receptor co-precipitates with RGSZ1 and influence mu receptor signaling by acting as effector antagonists [J. Garzon, M. Rodriguez-Munoz, P. Sanchez-Blazquez, Neuropharmacology 48 (2005) 853., J. Garzon, M. Rodriguez-Munoz, A. Lopez-Fando, P. Sanchez-Blazquez Neuropsychopharmacology 30 (2005) 1632.]. Inhibition of cAMP by mu opioid receptor was significantly reduced by RGSZ1 and this effect was enhanced in combination with PKCI-1. Our studies thus provide a link between the previous observations mentioned above and indicate that the major function of PKCI-1 is to modulate mu opioid receptor signaling pathway along with RGSZ1, rather than directly mediating the Gαz RGSZ1 interaction.

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Cell Biology
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