Cytokine and Cytokine Receptor Pleiotropy and Redundancy

Ozaki, Katsutoshi; Leonard, Warren J.

doi:10.1074/jbc.r200003200

Cited by 297 publications

(213 citation statements)

References 69 publications

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“…Thus, gene disruption is compensated by the redundant protein(s) and the relevant biological function is preserved (1)(2)(3)(4). This important phenomenon is widely discussed in different scientific circles, but is far from understood at the molecular level.…”

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confidence: 99%

RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: A different interpretation of redundancy

Nedvetzki

Gonen

Assayag

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

181

175

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We report here that joint inflammation in collagen-induced arthritis is more aggravated in CD44-knockout mice than in WT mice, and we provide evidence for molecular redundancy as a causal factor. Furthermore, we show that under the inflammatory cascade, RHAMM (receptor for hyaluronan-mediated motility), a hyaluronan receptor distinct from CD44, compensates for the loss of CD44 in binding hyaluronic acid, supporting cell migration, up-regulating genes involved with inflammation (as assessed by microarrays containing 13,000 cDNA clones), and exacerbating collagen-induced arthritis. Interestingly, we further found that the compensation for loss of the CD44 gene does not occur because of enhanced expression of the redundant gene (RHAMM), but rather because the loss of CD44 allows increased accumulation of the hyaluronic acid substrate, with which both CD44 and RHAMM engage, thus enabling augmented signaling through RHAMM. This model enlightens several aspects of molecular redundancy, which is widely discussed in many scientific circles, but the processes are still ill defined

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mentioning

confidence: 99%

RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: A different interpretation of redundancy

Nedvetzki

Gonen

Assayag

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

181

175

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“…IL-11 binds with low affinity to a specific IL-11Rα chain that is incapable of eliciting an intracellular signal. To that end, the promiscuous signal-transducing gp130 β-chain is recruited, which also participates in the receptor complex for other type I cytokines including IL-6, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), and cardiotrophin-1 (CT-1) (Ozaki and Leonard 2002). The stoichiometry of the functional IL-11 receptor complex is a hexamer that consists of two molecules each of IL-11, IL-11Rα, and gp130 (Barton et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Multiple and highly divergent IL-11 genes in teleost fish

et al. 2005

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Interleukin-11 (IL-11) is a key cytokine in the regulation of proliferation and differentiation of hematopoietic progenitors and is also involved in bone formation, adipogenesis, and protection of mucosal epithelia. Despite this prominent role in diverse physiological processes, IL-11 has been described in only four mammalian species, and recently, in rainbow trout (Oncorhynchus mykiss). Here we report the presence of IL-11 in common carp (Cyprinus carpio), a bony fish species related to zebrafish. IL-11 is expressed in most carp organs and tissues. In vitro expression of IL-11 in cultured macrophages is enhanced by stimulation with lipopolysaccharide and is markedly inhibited by cortisol. A detailed and systematic scan of several fish genome databases confirms that IL-11 is present in all fish, but also reveals the presence of a second, substantially different IL-11 gene in the genomes of phylogenetically distant fish species. We designated both fish paralogues IL-11a and IL-11b. Although sequence identity between fish IL-11a and IL-11b peptides is low, the conservation of their gene structures supplemented by phylogenetic analyses clearly illustrate the orthology of both IL-11a and IL-11b genes of fish with mammalian IL-11. The presence of IL-11 genes in fish demonstrates its importance throughout vertebrate evolution, although the presence of duplicate and divergent IL-11 genes differs from the single IL-11 gene that exists in mammals.

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“…Figure S5), nine additional developmental signaling pathways (including adherens junction, apoptosis, axon guidance, cell cycle, cytokine-cytokine receptor interaction, dorsal-ventral axis formation, ErbB, focal adhesion, and gap junction signaling pathways) were regulated by the Yamanaka factors ( Figure 6C). On the basis of the reported functions of these pathways [34][35][36][37][38][39][40], we hypothesize that they may function as the signaling pathways important for ES cell pluripotency and iPS cell induction. Collectively, our results indicate that Yamanaka factors regulate about 16 out of the 25 developmental signaling pathways in the KEGG pathway Mus musculus database.…”

Section: Pathway Analysis Of the Developmental Signaling Network Regumentioning

confidence: 99%

Yamanaka factors critically regulate the developmental signaling network in mouse embryonic stem cells

et al. 2008

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npg Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells, and their overexpression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency. However, systemic analysis of the signaling pathways regulated by Yamanaka factors has not yet been fully described. In this study, we identified the target promoters of endogenous Yamanaka factors on a whole genome scale using ChIP (chromatin immunoprecipitation)-on-chip in E14.1 mouse ES cells, and we found that these four factors co-occupied 58 promoters. Interestingly, when Oct4 and Sox2 were analyzed as core factors, Klf4 functioned to enhance the core factors for development regulation, whereas c-Myc seemed to play a distinct role in regulating metabolism. The pathway analysis revealed that Yamanaka factors collectively regulate a developmental signaling network composed of 16 developmental signaling pathways, nine of which represent earlier unknown pathways in ES cells, including apoptosis and cellcycle pathways. We further analyzed data from a recent study examining Yamanaka factors in mouse ES cells. Interestingly, this analysis also revealed 16 developmental signaling pathways, of which 14 pathways overlap with the ones revealed by this study, despite that the target genes and the signaling pathways regulated by each individual Yamanaka factor differ significantly between these two datasets. We suggest that Yamanaka factors critically regulate a developmental signaling network composed of approximately a dozen crucial developmental signaling pathways to maintain the pluripotency of ES cells and probably also to induce pluripotent stem cells.

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Cytokine and Cytokine Receptor Pleiotropy and Redundancy

Cited by 297 publications

References 69 publications

RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: A different interpretation of redundancy

RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: A different interpretation of redundancy

Multiple and highly divergent IL-11 genes in teleost fish

Yamanaka factors critically regulate the developmental signaling network in mouse embryonic stem cells

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