Rack1 Binds HIV-1 Nef and Can Act as a Nef–Protein Kinase C Adaptor

Gallina, Andrea; Rossi, Federica; Milanesi, G.

doi:10.1006/viro.2001.0855

Cited by 38 publications

(26 citation statements)

References 69 publications

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“…Therefore, we postulate that the interaction takes place at sorting endosomes or at subdomains in the plasma membrane (e.g. clathrin-coated pits, where RACK1 was previously reported to localize in HEK-293 cells) (34).…”

Section: Discussionmentioning

confidence: 93%

“…Interaction of NHE9 with RACK1 Is Topologically Possible-RACK1 is localized to the cytoplasm (31)(32)(33)(34)(35)(36)(37). Therefore, interaction with NHE9 would be possible only if the C terminus of NHE9 is exposed to the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

“…Colocalization of RACK1 and NHE6 was further investigated by double immunofluorescent staining. The reported subcellular localization of RACK1 differs depending on the cell line (31)(32)(33)(34)(35)(36)(37). As shown in Fig.…”

Section: Rack1 Binds Other Organellar Nhes In Vitro and In Vivo-mentioning

confidence: 96%

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Cell Surface Levels of Organellar Na+/H+ Exchanger Isoform 6 Are Regulated by Interaction with RACK1

Ohgaki

Fukura

Matsushita

et al. 2008

Journal of Biological Chemistry

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In mammalian cells, four Na؉ /H ؉ exchangers (NHE6 -NHE9) are localized to intracellular compartments. NHE6 and NHE9 are predominantly localized to sorting and recycling endosomes, NHE7 to the trans-Golgi network, and NHE8 to the mid-trans-Golgi stacks. The unique localization of NHEs may contribute to establishing organelle-specific pH values and ion homeostasis in cells. Mechanisms underlying the regulation and targeting of organellar NHEs are largely unknown. We identified an interaction between NHE9 and RACK1 (receptor for activated C kinase 1), a cytoplasmic scaffold protein, by yeast two-hybrid screening using the NHE9 C terminus as bait. The NHE9 C terminus is exposed to the cytoplasm, verifying that the interaction is topologically possible. The binding region was further delineated to the central region of the NHE9 C terminus. RACK1 also bound NHE6 and NHE7, but not NHE8, in vitro. Endogenous association between NHE6 and RACK1 was confirmed by co-immunoprecipitation and co-localization in HeLa cells. The luminal pH of the recycling endosome was elevated in RACK1 knockdown cells, accompanied by a decrease in the amount of NHE6 on the cell surface, although the total level of NHE6 was not significantly altered. These results indicate that RACK1 plays a role in regulating the distribution of NHE6 between endosomes and the plasma membrane and contributes to maintaining luminal pH of the endocytic recycling compartments.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Cell Surface Levels of Organellar Na+/H+ Exchanger Isoform 6 Are Regulated by Interaction with RACK1

Ohgaki

Fukura

Matsushita

et al. 2008

Journal of Biological Chemistry

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“…Because this region is sufficient for binding, it is conceivable that folding of RACK1 into a complete seven-bladed-propeller structure is not essential for its association with FAN. The very same region of RACK1 has also been implicated in its binding to the integrin ␤ subunit and to the HIV-1 Nef protein as well as to the cAMP-specific phosphodiesterase isoform PDE4D5 (23,33,55). Obviously, this region constitutes an interface through which RACK1 can interact with various different proteins.…”

Section: Discussionmentioning

confidence: 99%

Interaction with Factor Associated with Neutral Sphingomyelinase Activation, a WD Motif-Containing Protein, Identifies Receptor for Activated C-Kinase 1 as a Novel Component of the Signaling Pathways of the p55 TNF Receptor

Tcherkasowa

Adam‐Klages

Kruse

et al. 2002

The Journal of Immunology

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Factor associated with neutral sphingomyelinase activation (FAN) represents a p55 TNFR (TNF-R55)-associated protein essential for the activation of neutral sphingomyelinase. By means of the yeast interaction trap system, we have identified the scaffolding protein receptor for activated C-kinase (RACK)1 as an interaction partner of FAN. Mapping studies in yeast revealed that RACK1 is recruited to the C-terminal WD-repeat region of FAN and binds to FAN through a domain located within WD repeats V to VII of RACK1. Our data indicate that binding of both proteins is not mediated by linear motifs but requires folding into a secondary structure, such as the multibladed propeller characteristic of WD-repeat proteins. The interaction of FAN and RACK1 was verified in vitro by glutathione S-transferase-based coprecipitation assays as well as in eukaryotic cells by coimmunoprecipitation experiments. Colocalization studies in transfected cells suggest that TNF-R55 forms a complex with FAN and that this complex recruits RACK1 to the plasma membrane. Furthermore, activation of N-SMase by TNF was strongly enhanced when RACK1, FAN, and a noncytotoxic TNF-R55 mutant were expressed concurrently, suggesting RACK1 as a modulator of N-SMase activation. Together, these findings implicate RACK1 as a novel component of the signaling pathways of TNF-R55.

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“…Smith et al reported that A73 protein translated from CST (BART BARF0) transcript RNA of EpsteinBarr virus is able to interact with cellular RACK1 and modulate signaling from protein kinase C and Src tyrosine kinase to regulate cancer growth, such as nasopharyngeal carcinoma (19). It has also been noted that RACK1 acts as a human immunodeficiency virus Nef intracellular docking site, bringing Nef and protein kinase C together (a Nef-protein kinase C adaptor) (8). Sang et al demonstrated that RACK1 physically interacts with adenovirus E1A and acts as a repressor of E1A, possibly by antagonizing the effects of E1A on host gene transcription (18).…”

Section: Discussionmentioning

confidence: 99%

Association of Mumps Virus V Protein with RACK1 Results in Dissociation of STAT-1 from the Alpha Interferon Receptor Complex

Kubota

Yokosawa

Yokota

et al. 2002

J Virol

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It has been reported that mumps virus protein V or the C-terminal Cys-rich region of protein V (Vsp) is associated with blocking of the interferon (IFN) signal transduction pathway through a decrease in STAT-1 production. The intracellular target of the V protein was investigated by using a two-hybrid screening system with Vsp as bait. Full-length V protein and Vsp were able to bind to RACK1, and the interaction did not require two WD domains, WD1 and WD2, in RACK1. A significant interaction between V protein and RACK1 was also demonstrated in cells persistently infected with mumps virus (FLMT cells), and the formation of the complex was not affected by treatment with IFN. On the other hand, in uninfected cells, STAT-1 was associated with the long form of the ␤ subunit of the alpha IFN receptor, and this association was mediated by the function of RACK1 as an adaptor protein. Immunoprecipitation and glutathione S-transferase pull-down experiments revealed that the association of RACK1 or mumps virus V protein with the IFN receptor was undetectable in mumps virus-infected cells. Furthermore, RACK1 interacted with mumps virus V protein with a higher affinity than STAT-1 did. Therefore, it is suggested that mumps virus V protein has the ability to interact strongly with RACK1 and consequently to bring about the disruption of the complex formed from STAT-1, RACK1, and the IFN receptor.Many functions of interferon (IFN) are induced by activation of the JAK (Janus protein kinase)/STAT (proteins in the family of signal tranducers and activators of transcription) signaling pathway. In the alpha IFN (IFN-␣) signaling pathway, STAT-2 and STAT-1␣ are phosphorylated by IFN-␣ to form the IFN-stimulated gene factor 3 complex through activation of the tyrosine kinases Jak-1 and Tyk-2. The IFN-stimulated gene factor 3 complex formed from the STAT-1␣, STAT-2, and IFN regulatory factor-9 (IRF-9) components strongly binds to the consensus sequence of the IFN-␣-stimulated response element in the promoter region of the IFN-stimulated gene. Gamma interferon (IFN-␥) mediates the phosphorylation of STAT-1␣ to form a homodimer, the IFN-␥-activated factor complex, through the activation of Jak-1 and Jak-2 caused by tyrosine phosphorylation. The IFN-␥-activated factor complex binds to the IFN-␥-activated sequence element in the regulatory region of IFN-␥-inducible genes. Tyrosine kinase Jak-1 and STAT-1␣ are the essential components of the IFN-␣ and IFN-␥ signaling pathway.The antiviral activity of IFN, whose function is largely due to the intracellular induction of 2Ј,5Ј-oligoadenylate synthetase, double-stranded RNA-activated protein kinase, and Mx protein through the JAK/STAT pathway, is the most important defense mechanism against viral infection. However, it has been reported that some viruses have the ability to break down IFN functions through suppression of the IFN signal transduction pathway and to inhibit antiviral protein or enzyme, 2Ј,5Ј-oligoadenylate synthetase, or double-stranded RNA-activated protein kinase activity (4, 9,...

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Rack1 Binds HIV-1 Nef and Can Act as a Nef–Protein Kinase C Adaptor

Cited by 38 publications

References 69 publications

Cell Surface Levels of Organellar Na+/H+ Exchanger Isoform 6 Are Regulated by Interaction with RACK1

Cell Surface Levels of Organellar Na+/H+ Exchanger Isoform 6 Are Regulated by Interaction with RACK1

Interaction with Factor Associated with Neutral Sphingomyelinase Activation, a WD Motif-Containing Protein, Identifies Receptor for Activated C-Kinase 1 as a Novel Component of the Signaling Pathways of the p55 TNF Receptor

Association of Mumps Virus V Protein with RACK1 Results in Dissociation of STAT-1 from the Alpha Interferon Receptor Complex

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