The WD Motif-Containing Protein RACK-1 Functions as a Scaffold Protein Within the Type I IFN Receptor-Signaling Complex

Usacheva, Anna; Tian, Xinxin; Sandoval, Raudel; Salvi, Debra; Levy, David E.; Colamonici, Oscar R.

doi:10.4049/jimmunol.171.6.2989

Cited by 28 publications

(19 citation statements)

References 40 publications

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“…Until present, the only scaffold protein known to participate in type I IFN signaling is RACK1, which promotes the JAK-STAT pathway by forming a multiprotein complex consisting of the IFN␣ receptor, STAT1, JAK1, and TYK2 (Usacheva et al, 2003). Thus, filamin B represents the first scaffold that was shown in this study to mediate type I IFN-induced MAPK signaling.…”

Section: Discussionmentioning

confidence: 63%

Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH₂-terminal Kinase Signaling Pathway

Jeon

Choi

Lee

et al. 2008

MBoC

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INTRODUCTIONInterferons (IFNs) are a family of cytokines that mediate antiviral, antiproliferative, antitumor, and immunomodulatory responses (Boehm et al., 1997;Stark et al., 1998;Kalvakolanu, 2000;Sen, 2000;Taniguchi and Takaoka, 2001;Platanias, 2005). IFNs are divided into two groups: type I (including IFN␣ and IFN␤) and type II (IFN␥). Of these, type I IFNs mediate the pleiotropic biological effects by activating tyrosine kinase (TYK)-2 and Janus tyrosine kinase (JAK)-1 kinases, which are associated with type I interferon receptor (IFNAR) 1 and IFNAR2 subunits of type I IFN receptors, respectively. The activated JAK kinases regulate downstream engagement of multiple signal transducer and activator of transcription (STAT) proteins that translocate to the nucleus to induce gene transcription via binding to the promoters of IFN-stimulated genes.The first signaling pathway shown to be activated by IFNs is JAK-STAT pathway, but it becomes evident that other IFN-regulated signaling cascades are required for the generation of pleiotropic responses to IFNs. Examples of the cascades that operate independently of JAK-STAT pathway include mitogen-activated protein kinase (MAPK) signaling pathways that link a variety of extracellular signals to cellular responses as diverse as proliferation, differentiation, and apoptosis (Whitmarsh and Davis, 1998;Garrington and Johnson, 1999;Schaeffer and Weber, 1999;Widmann et al., 1999). Mitogen-activated protein (MAP) kinases are classified into four main groups: p38, extracellular signal-regulated kinase (ERK)1/2, ERK5, and JNK families (Wang and Tournier, 2006). Of MAPK pathways, p38 pathway has most extensively been studied for its role in the generation of IFN-mediated responses. p38 is phosphorylated and activated in a type I IFN-dependent manner and the inhibition of p38 activity blocks IFN␣-dependent transcription of genes that are regulated by IFN-stimulated response elements (ISREs) (Goh et al., 1999;Uddin et al., 1999). Moreover, disruption of the p38␣ gene results in defective transcription of genes that are regulated by ISREs and/or gamma interferon activated sequence elements (Li et al., 2004). The small GTPase Rac1 is activated in a type I IFN-dependent manner, and its function is required for downstream engagement of p38 pathway (Uddin et al., 2000). Type I IFNs also induce the activation of mitogen-activated kinase kinase (MKK) 3 and MKK6 that are essential for p38 activation (Li et al., 2005). Type I IFNs have also been shown to activate JNK for the induction of apoptosis in some lymphoma cells (Yanase et al., 2005), but the downstream signaling cascade that mediates type I IFN-induced JNK activation remains unknown. In addition, it has been reported that ERK2 is activated by type I IFNs and in response to viral infection, and the expression of dominant-negative (dn) ERK2 inhibits type I IFN-induced transcription (David et al., 1995; This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -06 -0576) on Se...

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Section: Discussionmentioning

confidence: 63%

Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH₂-terminal Kinase Signaling Pathway

Jeon

Choi

Lee

et al. 2008

MBoC

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“…This is consistent with previous studies suggesting that the WD domain dominantly interferes with coronin-1 function (Mishima and Nishida, 1999). WD domains are predicted to act as multimolecular scaffolding domains by bringing together interacting proteins on a single surface (Usacheva et al, 2003). The isolated WD domains are likely to interfere with normal cell function by scavenging interacting proteins away from the endogenous, full-length coronin.…”

Section: Discussionmentioning

confidence: 99%

Coronin-1 Function Is Required for Phagosome Formation

Yan

Collins

Grinstein

et al. 2005

MBoC

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Coronin-1 is an actin-associated protein whose function in actin dynamics has remained obscure. All coronin proteins have a variable N-terminal domain, followed by WD repeats and a C-terminal coiled-coil dimerization domain. Transfection of coronin-1-GFP into RAW 264.7 cells revealed that coronin rapidly and transiently associates with the phagosome. To determine if coronin is involved in mammalian phagocytosis we used a dominant-negative approach by expressing only the central WD domains. However, this caused cell rounding and dissociation from the substratum, hampering analysis of their phenotype. We therefore developed TAT-fusion constructs of coronin-1 WD domains to acutely introduce the recombinant protein fragment into live cells. We show that although TAT-WD has no effect on binding of opsonized RBCs to RAW 264.7 cells, receptor clustering or several downstream signaling events, lamellipodial extensions, and actin accumulation at the base of the bound particle were diminished. Furthermore, Arp3 accumulation at the phagosome was impaired after TAT-WD treatment. Interestingly, whereas coronin-1 also accumulates at the sites of actin remodeling associated with Salmonella invasion, TAT-WD had no effect on this process. Together, our data demonstrates that coronin-1 is required for an early step in phagosome formation, consistent with a role in actin polymerization.

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“…27) that allows it to bind multiple proteins simultaneously. Indeed, in the interferon system RACK1 forms the backbone of a multiprotein complex that includes the IFN receptor, STAT1, Janus kinase 1, and tyrosine kinase 2 (52). A list of proteins that have been found to associate with RACK1 would contain at least 25 members (32) including two other channels: the NMDA receptor (57) and the GABA A receptor (9).…”

Section: Discussionmentioning

confidence: 99%

RACK1 is a BK_Ca channel binding protein

Isacson¹,

Lü²,

Karas³

et al. 2007

American Journal of Physiology-Cell Physiology

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Isacson CK, Lu Q, Karas RH, Cox DH. RACK1 is a BKCa channel binding protein. Am J Physiol Cell Physiol 292: C1459 -C1466, 2007. First published January 31, 2006; doi:10.1152/ajpcell.00322.2006.-The large conductance calcium-activated potassium channel, or BKCa channel, plays an important feedback role in a variety of physiological processes, including neurotransmitter release and smooth muscle contraction. Some reports have suggested that this channel forms a stable complex with regulators of its function, including several kinases and phosphatases. To further define such signaling complexes, we used the yeast two-hybrid system to screen a human aorta cDNA library for proteins that bind to the BK Ca channel's intracellular, COOH-terminal "tail". One of the interactors we identified is the protein receptor for activated C kinase 1 (RACK1). RACK1 is a member of the WD40 protein family, which also includes the G protein ␤-subunits. Consistent with an important role in BK Ca-channel regulation, RACK1 has been shown to be a scaffolding protein that interacts with a wide variety of signaling molecules, including cSRC and PKC. We have confirmed the interaction between RACK1 and the BK Ca channel biochemically with GST pull-down and coimmunoprecipitation experiments. We have observed some co-localization of RACK1 with the BK Ca channel in vascular smooth muscle cells with immunocytochemical experiments, and we have found that RACK1 has effects on the BK Ca channel's biophysical properties. Thus RACK1 binds to the BK Ca channel and it may form part of a BK Ca-channel regulatory complex in vascular smooth muscle.calcium-activated potassium channel; protein kinase C; smooth muscle LARGE CONDUCTANCE Ca 2ϩ -activated potassium channels (BK Ca channels) are uniquely sensitive to both intracellular Ca 2ϩ concentration and membrane voltage. They are found in many tissues, and they are particularly abundant in nerve and smooth muscle, where they provide feedback control over the Ca 2ϩ and voltage-dependent processes of neurotransmitter release and smooth muscle contraction. In the nervous system, BK Ca channels are activated by Ca 2ϩ entering through nearby calcium channels (26,39,41), and their activity regulates the duration of the nerve-terminal action potential (20,40,47). In smooth muscle, they are activated by Ca 2ϩ released from internal stores (6,30). This causes the membrane potential to hyperpolarize and Ca 2ϩ entry through voltage-gated Ca 2ϩ channels to decrease (17,30,31). In both cases, BK Ca channels regulate tissue function indirectly by regulating Ca 2ϩ entry. Given the BK Ca channel's role as an important regulator of Ca 2ϩ -dependent processes, it is perhaps not surprising that the BK Ca channel itself is regulated by second messengers in addition to calcium, including protein phosphatases (8, 55, 56), heterotrimeric GTP binding proteins (18,19), and protein kinases (36 -38). The BK Ca channel's pore-forming ␣-subunit is phosphorylated by cAMP-dependent protein kinase (PKA) (50, 58), protein kinase C (PKC) (38...

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The WD Motif-Containing Protein RACK-1 Functions as a Scaffold Protein Within the Type I IFN Receptor-Signaling Complex

Cited by 28 publications

References 40 publications

Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH₂-terminal Kinase Signaling Pathway

Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH₂-terminal Kinase Signaling Pathway

Coronin-1 Function Is Required for Phagosome Formation

RACK1 is a BK_Ca channel binding protein

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The WD Motif-Containing Protein RACK-1 Functions as a Scaffold Protein Within the Type I IFN Receptor-Signaling Complex

Cited by 28 publications

References 40 publications

Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH2-terminal Kinase Signaling Pathway

Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH2-terminal Kinase Signaling Pathway

Coronin-1 Function Is Required for Phagosome Formation

RACK1 is a BKCa channel binding protein

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Resources

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Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH₂-terminal Kinase Signaling Pathway

Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH₂-terminal Kinase Signaling Pathway

RACK1 is a BK_Ca channel binding protein