Ca<sup>2+</sup>/Calmodulin-Dependent Protein Kinase II Is a Modulator of CARMA1-Mediated NF-κB Activation

Ishiguro, Kazuhiro; Green, Todd; Rapley, Joseph; Wachtel, Heather; Giallourakis, Cosmas; Landry, Aimee; Cao, Zhiwei; Lu, Naifang; Ando, Takafumi; Goto, Hidemi; Daly, Mark J.; Xavier, Ramnik J.

doi:10.1128/mcb.02469-05

Cited by 91 publications

(75 citation statements)

References 54 publications

(71 reference statements)

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“…4C). Consistent with our findings, CARMA1 was reported to be required for Akt-mediated NF-B activation in T cells (17).…”

Section: Discussionsupporting

confidence: 82%

“…Nevertheless, our data suggest that there is a PKC--independent pathway that induces formation of the CBM complex. Indeed, either Akt or CaM kinase II may associate with CARMA1 or induce CARMA1 phosphorylation (17,33), which may represent this alternative pathway. In support of this notion, the inhibition of Akt blocks CBM complex formation and the subsequent coupling of PKC--IKKs to the Bcl10-MALT1 complex (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

Qiao

Molinero

et al. 2008

Molecular and Cellular Biology

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“…4C). Consistent with our findings, CARMA1 was reported to be required for Akt-mediated NF-B activation in T cells (17).…”

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

Qiao

Molinero

et al. 2008

Molecular and Cellular Biology

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“…Moreover, some kinases may contribute to CARMA1 phosphorylation outside the linker region. Consistent with this notion, calmodulin-dependent protein kinase II (CaMKII) is recruited to the immunological synapse following TCR stimulation, and phosphorylates CARMA1 on Ser109 [72]. Mutation of Ser109 to Ala residue in CARMA1 impairs its biological function [72].…”

Section: The Mechanism Of T Cell Receptor-induced Car-ma1 Activationmentioning

confidence: 71%

“…Consistent with this notion, calmodulin-dependent protein kinase II (CaMKII) is recruited to the immunological synapse following TCR stimulation, and phosphorylates CARMA1 on Ser109 [72]. Mutation of Ser109 to Ala residue in CARMA1 impairs its biological function [72]. Once activated, CARMA1 recruits the IKK complex [60,61] and other signaling molecules (Table 1) [63,[67][68][69]73], including Bcl10 and its pre-associated partner MALT1 [60,61,74].…”

Section: The Mechanism Of T Cell Receptor-induced Car-ma1 Activationmentioning

confidence: 71%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

173

201

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The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB.

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“…Engagement of the TCR triggers canonical NF-B activation by PKC-driven formation of the CBM complex (containing CARMA1, Bcl10, and MALT1) (8,9,61,62). During formation of the CBM complex, Ca 2ϩ has been implicated in CARMA1 and Bcl10 phosphorylation via Calmodulin kinase II (63)(64)(65) and Bcl10 dephosphorylation by Calcineurin A (10,42). Our data confirm this general modulatory role for Ca 2ϩ in steps proximal to IKK activation and IB␣ degradation.…”

Section: Discussionmentioning

confidence: 99%

T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry

Liu

Berry

Ruthel

et al. 2016

Journal of Biological Chemistry

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T cell activation following antigen binding to the T cell receptor (TCR) involves the mobilization of intracellular Ca2؉ to activate the key transcription factors nuclear factor of activated T lymphocytes (NFAT) and NF-B. 2؉ -dependent checkpoint in TCR-induced NF-B signaling that has broad implications for the control of immune cell development and T cell functional specificity. Activation of T cells following antigen binding to the T cell antigen receptor (TCR)3 induces diverse lineage-and fate-specific proinflammatory and immune-modulatory responses. Central to these responses is the induction of quantitatively distinct intracellular Ca 2ϩ signals and their selective activation of the key transcription factors NFAT and NF-B (1-6). The mechanism by which Ca 2ϩ controls NFAT activation in lymphocytes is well established (7). In contrast, although Ca 2ϩ has been implicated in TCR-induced NF-B signaling (8 -10), how Ca 2ϩ regulates NF-B activity is largely unexplored and represents a significant gap in our understanding of transcriptional control of T cell development, activation, and functional specificity.In resting T cells, classical NF-B consists of heterodimers of p50/p65 or p50/c-Rel that are retained in the cytosol by members of the inhibitory family of IB proteins (11, 12). Following TCR engagement, IB kinase (IKK)-mediated phosphorylation triggers the ubiquitination and proteasomal degradation of IB␣, releasing p50/p65 and p50/c-Rel, which localize to the nucleus to initiate transcription of crucial immune-regulatory, proinflammatory, and proproliferative genes (13-30). Although TCR-mediated Ca 2ϩ mobilization has been implicated in proximal steps of NF-B activation (8 -10), the precise mechanisms and source of Ca 2ϩ that regulate nuclear localization and transcriptional activation of NF-B are poorly defined. It is well established that TCR signaling induces inositol 1,4,5-trisphosphate-mediated depletion of Ca 2ϩ from the endoplasmic reticulum (ER). A resulting Ca 2ϩ dissociation from the ER membrane protein stromal interaction molecule 1 (STIM1) triggers its oligomerization and relocalization to ER membrane domains juxtaposed to the plasma membrane (31-33), where STIM1 physically gates Orai (also known as Ca 2ϩ release-activated Ca 2ϩ ) channels, allowing extracellular Ca 2ϩ to enter the cell (34,35). However, it is not known whether Ca 2ϩ control of TCR-induced NF-B signaling requires STIM1-and Orai1-mediated Ca 2ϩ influx or whether the initial release of Ca 2ϩ from the ER is sufficient for classical NF-B activation.In this study, we sought to determine both the source and mechanism of Ca 2ϩ control of antigen receptor-induced NF-B activation in T cells. We show that influx of extracellular Ca 2ϩ via STIM1 and Orai is critical for TCR-but not TNFinduced IB␣ degradation and NF-B activation. Importantly, we also demonstrate that Ca 2ϩ -dependent, PKC␣-mediated phosphorylation of p65 critically regulates its nuclear localization and transcriptional activation following TCR engagement. Thus, our findings ...

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Ca²⁺/Calmodulin-Dependent Protein Kinase II Is a Modulator of CARMA1-Mediated NF-κB Activation

Cited by 91 publications

References 54 publications

T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry

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Ca2+/Calmodulin-Dependent Protein Kinase II Is a Modulator of CARMA1-Mediated NF-κB Activation

Cited by 91 publications

References 54 publications

T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry

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Ca²⁺/Calmodulin-Dependent Protein Kinase II Is a Modulator of CARMA1-Mediated NF-κB Activation