Characterization of a Novel Ras-Binding Protein Ce-FLI-1 Comprising Leucine-Rich Repeats and Gelsolin-like Domains

Goshima, Masahiro; Kariya, Ken-ichi; Yamawaki-Kataoka, Yuriko; Okada, Tomoyo; Shibatohge, Mitsushige; Shima, Fumi; Fujimoto, Etsuko; Kataoka, Tohru

doi:10.1006/bbrc.1999.0420

Cited by 54 publications

(75 citation statements)

References 42 publications

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“…Perhaps Fliih undergoes some kind of posttranslational modification or becomes released from some kind of inhibitor(s) upon stimulation, which then interacts with MyD88 and TLR4 to terminate the signaling. It has been reported that Fliih interacts with Ras protein via the LRR domain (40,41). Ras participates in CpG oligodeoxynucleotide signaling through association with TLR9 and promotion of IRAK/TRAF6 complex formation in macrophages (42).…”

Section: Discussionmentioning

confidence: 99%

Flightless I Homolog Negatively Modulates the TLR Pathway

Wang

Chuang

Ronni

et al. 2006

The Journal of Immunology

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To date, much of our knowledge about the signaling networks involved in the innate immune response has come from studies using nonphysiologic model systems rather than actual immune cells. In this study, we used a dual-tagging proteomic strategy to identify the components of the MyD88 signalosome in murine macrophages stimulated with lipid A. This systems approach revealed 16 potential MyD88-interacting partners, one of which, flightless I homolog (Fliih) was verified to interact with MyD88 and was further characterized as a negative regulator of the TLR4-MyD88 pathway. Conversely, a reduction in endogenous Fliih by small-interfering RNA enhanced the activation of NF-κB, as well as cytokine production by LPS. Results from immunoprecipitation and a two-hybrid assay further indicated that Fliih directly interfered with the formation of the TLR4-MyD88 signaling complex. These results in turn suggest a new basis for the regulation of the TLR pathway by Fliih.

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Section: Discussionmentioning

confidence: 99%

Flightless I Homolog Negatively Modulates the TLR Pathway

Wang

Chuang

Ronni

et al. 2006

The Journal of Immunology

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“…Consistent with having the gelsolin domain, the human and Caenorhabditis elegans FLI-1 proteins bind to both actin monomers (G-actin) and actin filaments (F-actin) in vitro and possess F-actin-serving activity (Liu and Yin 1998;Goshima et al 1999). Unlike other gelsolin family proteins, the actin-binding and severing activity of Fli I appears to be calcium independent (Goshima et al 1999). Consistently, the residues essential for calcium binding in the gelsolin region of the other gelsolin family proteins are not conserved in Fli I (Goshima et al 1999).…”

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confidence: 96%

“…Unlike other gelsolin family proteins, the actin-binding and severing activity of Fli I appears to be calcium independent (Goshima et al 1999). Consistently, the residues essential for calcium binding in the gelsolin region of the other gelsolin family proteins are not conserved in Fli I (Goshima et al 1999).…”

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confidence: 96%

“…The LRR motif is known to be involved in protein-protein or proteinlipid interactions, suggesting a role for Fli I in linking the actin cytoskeleton with the signal transduction pathways (Claudianos and Campbell 1995;Campbell et al 1997). Consistent with having the gelsolin domain, the human and Caenorhabditis elegans FLI-1 proteins bind to both actin monomers (G-actin) and actin filaments (F-actin) in vitro and possess F-actin-serving activity (Liu and Yin 1998;Goshima et al 1999). Unlike other gelsolin family proteins, the actin-binding and severing activity of Fli I appears to be calcium independent (Goshima et al 1999).…”

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confidence: 99%

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The Flightless I Homolog, fli-1, Regulates Anterior/Posterior Polarity, Asymmetric Cell Division and Ovulation During Caenorhabditis elegans Development

et al. 2007

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Flightless I (Fli I) is an evolutionarily conserved member of the gelsolin family, containing actin-binding and severing activity in vitro. The physiological function of Fli I during animal development remains largely undefined. In this study, we reveal a key role of the Caenorhabditis elegans Fli I homolog, fli-1, in specifying asymmetric cell division and in establishing anterior-posterior polarity in the zygote. The fli-1 gene also regulates the cytokinesis of somatic cells and the development of germline and interacts with the phosphoinositol-signaling pathway in the regulation of ovulation. The fli-1 reporter gene shows that the localization of FLI-1 coincides with actin-rich regions and that the actin cytoskeleton is impaired in many tissues in the fli-1 mutants. Furthermore, the function of fli-1 in C. elegans can be functionally substituted by the Drosophila Fli I. Our studies demonstrate that fli-1 plays an important role in regulating the actin-dependent events during C. elegans development.

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“…In the nucleus, Fli-I acts as a cofactor in the nuclear receptor complex and facilitates the transcriptional activation of nuclear receptors such as the estrogen receptor and androgen receptor (12,13). Cytosolic Fli-I binds to small GTPase Ras and localizes to the actin-based structures, probably through its gelsolin-like domain (14,15). Fli-I also binds to proinflammatory caspases (caspase-1 and caspase-11) and suppresses caspase-1-mediated interleukin-1␤ maturation (16).…”

mentioning

confidence: 99%