Transcriptional activation of c-Fos by constitutively active Gα16QL through a STAT1-dependent pathway

Lo, Rico K.H.; Wong, Yung Hou

doi:10.1016/j.cellsig.2006.04.004

Cited by 9 publications

(13 citation statements)

References 43 publications

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“…IL-6 is a potent inflammatory cytokine that directly activates STAT1 and STAT3. The production of IL-6 in CCL15-stimulated THP-1 cells and transfected HEK293 cells implied that CCR1/Ga 14/16 could also stimulate STAT1, which is in line with our previous study showing that the constitutively active mutant of Ga 16 can enhance the activity of STAT1 (19). Our demonstration of CCR1/Ga 14/16 -mediated STAT3 Tyr 705 phosphorylation leading to subsequent CXCL8 production is in agreement with the report that CXCL8 expression is transcriptionally upregulated by STAT3 in human melanoma cells (58).…”

Section: Discussionsupporting

confidence: 78%

“…CCR1 agonists were found to induce gene expression of the STAT-inducible protooncogene, c-fos (18). c-Fos expression and transcriptional activation is induced upon Ga 16 activation (19), and constitutively active mutants of Ga 14 and Ga 16 were demonstrated to enhance the activity of STAT3 in cotransfection systems (20,21). The coexistence of Ga 14/16 and CCR1, as well as their demonstrated functional coupling in THP-1 macrophage-like cells (2,(22)(23)(24)(25)(26), suggests that CCR1 may use Ga 14/16 to stimulate STAT3.…”

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confidence: 99%

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CCR1-Mediated STAT3 Tyrosine Phosphorylation and CXCL8 Expression in THP-1 Macrophage-like Cells Involve Pertussis Toxin-Insensitive Gα14/16 Signaling and IL-6 Release

Lee

Chui

Tam

et al. 2012

The Journal of Immunology

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Agonists of CCR1 contribute to hypersensitivity reactions and atherosclerotic lesions, possibly via the regulation of the transcription factor STAT3. CCR1 was demonstrated to use pertussis toxin-insensitive Gα14/16 to stimulate phospholipase Cβ and NF-κB, whereas both Gα14 and Gα16 are also capable of activating STAT3. The coexpression of CCR1 and Gα14/16 in human THP-1 macrophage-like cells suggests that CCR1 may use Gα14/16 to induce STAT3 activation. In this study, we demonstrated that a CCR1 agonist, leukotactin-1 (CCL15), could indeed stimulate STAT3 Tyr705 and Ser727 phosphorylation via pertussis toxin-insensitive G proteins in PMA-differentiated THP-1 cells, human erythroleukemia cells, and HEK293 cells overexpressing CCR1 and Gα14/16. The STAT3 Tyr705 and Ser727 phosphorylations were independent of each other and temporally distinct. Subcellular fractionation and confocal microscopy illustrated that Tyr705-phosphorylated STAT3 translocated to the nucleus, whereas Ser727-phosphorylated STAT3 was retained in the cytosol after CCR1/Gα14 activation. CCL15 was capable of inducing IL-6 and IL-8 (CXCL8) production in both THP-1 macrophage-like cells and HEK293 cells overexpressing CCR1 and Gα14/16. Neutralizing Ab to IL-6 inhibited CCL15-mediated STAT3 Tyr705 phosphorylation, whereas inhibition of STAT3 activity abolished CCL15-activated CXCL8 release. The ability of CCR1 to signal through Gα14/16 provides a linkage for CCL15 to regulate IL-6/STAT3–signaling cascades, leading to expression of CXCL8, a cytokine that is involved in inflammation and the rupture of atherosclerotic plaque.

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Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 99%

CCR1-Mediated STAT3 Tyrosine Phosphorylation and CXCL8 Expression in THP-1 Macrophage-like Cells Involve Pertussis Toxin-Insensitive Gα14/16 Signaling and IL-6 Release

Lee

Chui

Tam

et al. 2012

The Journal of Immunology

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“…-dependent (Offermanns et al 2001) or independent (PKCm in COS cells unpublished) PKC isoforms triggers several pathways, including those stimulating NFkb (Yang et al 2001), ERK , JNK (Heasley et al 1996) JAK (Lo & Wong 2006, Lo et al 2008, cSrc (Lee et al 2009). Small GTPases, such as Ras and Rho are indirectly modulated by G15, via TPR1 (Yu et al 2008, Su et al 2009) and p63RhoGEF (Yeung & Wong 2009) respectively.…”

Section: +mentioning

confidence: 99%

“…By this approach, direct activation of downstream effectors is achieved bypassing the GPCR. Ga15-Q212L promoted the activity of transcription factors like nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and signal transducer and activator of transcription 3 (STAT3) via PKC (Lo & Wong 2006, Lee & Wong 2009) and c-Src/mitogen-activated protein kinase (MAPK)-dependent pathway , Liu & Wong 2004Fig. 2).…”

Section: Getting Further Insights On G15 Biological Functionmentioning

confidence: 99%

The puzzling uniqueness of the heterotrimeric G15 protein and its potential beyond hematopoiesis

Giannone¹,

Malpeli

Lisi

et al. 2010

Journal of Molecular Endocrinology

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Heterotrimeric G proteins transduce the signals of the largest family of membrane receptors (G protein-coupled receptors, GPCRs) hence triggering the activation of a wide variety of physiological responses. G15 is a G protein characterized by a number of functional peculiarities that make its signaling exceptional: 1) it can couple a variety of Gs-, Gi/o-, and Gq-linked receptors to phospholipase C activation; 2) relatively to other G proteins, it is poorly affected by b-arrestin-dependent desensitization, the general mechanism that regulates GPCR function and 3) at the protein level, its expression is only detected in highly specific cell types (hematopoietic and epithelial cells). G15 a-subunit displays unique structural and biochemical properties, and is phylogenetically the most recent and divergent component of the Gaq/11 subfamily. All these aspects shed a mysterious light on G15 biological role, which remains substantially elusive. Thus, far, G15 signaling has been analyzed in the context of hematopoiesis. Here, we highlight observations supporting the view that G15 functions may extend further beyond the immune system. In addition, we describe puzzling aspects of G15 signaling that offer a novel perspective in the understanding of its physiological role.

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“…JNKs also phosphorylate and activate JunD and ATF-2 (45,46). By contrast, the kinases that regulate the activity of Fos proteins are not yet well characterized, although a plethora of candidates have been suggested (47)(48)(49).…”

Section: Genetics and Epigenetics In Respiratory Epithelium Carcinogementioning

confidence: 99%

The Activator Protein-1 Transcription Factor in Respiratory Epithelium Carcinogenesis

Karamouzis

Konstantinopoulos²,

Papavassiliou³

2007

Molecular Cancer Research

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Respiratory epithelium cancers are the leading cause of cancer-related death worldwide. The multistep natural history of carcinogenesis can be considered as a gradual accumulation of genetic and epigenetic aberrations, resulting in the deregulation of cellular homeostasis. Growing evidence suggests that crosstalk between membrane and nuclear receptor signaling pathways along with the activator protein-1 (AP-1) cascade and its cofactor network represent a pivotal molecular circuitry participating directly or indirectly in respiratory epithelium carcinogenesis. The crucial role of AP-1 transcription factor renders it an appealing target of future nuclear-directed anticancer therapeutic and chemoprevention approaches. In the present review, we will summarize the current knowledge regarding the implication of AP-1 proteins in respiratory epithelium carcinogenesis, highlight the ongoing research, and consider the future perspectives of their potential therapeutic interest. (Mol Cancer Res 2007;5(2):109 -20)

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Transcriptional activation of c-Fos by constitutively active Gα16QL through a STAT1-dependent pathway

Cited by 9 publications

References 43 publications

CCR1-Mediated STAT3 Tyrosine Phosphorylation and CXCL8 Expression in THP-1 Macrophage-like Cells Involve Pertussis Toxin-Insensitive Gα14/16 Signaling and IL-6 Release

CCR1-Mediated STAT3 Tyrosine Phosphorylation and CXCL8 Expression in THP-1 Macrophage-like Cells Involve Pertussis Toxin-Insensitive Gα14/16 Signaling and IL-6 Release

The puzzling uniqueness of the heterotrimeric G15 protein and its potential beyond hematopoiesis

The Activator Protein-1 Transcription Factor in Respiratory Epithelium Carcinogenesis

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