Association of STAT1, STAT3 and STAT5 proteins with the IL-2 receptor involves different subdomains of the IL-2 receptor β chain

Delespine-Carmagnat, Maryvonnick; Bouvier, Ghislaine; Bertoglio, Jacques

doi:10.1002/1521-4141(200001)30:1<59::aid-immu59>3.0.co;2-1

Cited by 39 publications

(10 citation statements)

References 37 publications

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“…IL-2 and IL-15 are known as important growth and survival factors for distinct populations of lymphocytes (3,25,30,31,62), and the observation in the present study that there is no stringent correlation between cytokine-mediated induction of pSTAT5 and marker gene expression (compare Figure 9 and Figure 11) may relate to the fact that cell growth/survival and cell functional activity are not identical processes. It should also be realized that mammalian IL-2 and IL-15 can activate more transcription factors than only their dominantly activated transcription factor STAT5 (15,17,61), and future studies should establish antibodies for allowing a more extensive analysis of activated transcription factors in fish. Future research in fish should also try to establish antibodies against potential receptors of the IL-2/15/15L family and other cell surface markers so that sensitive cell populations can be further characterized.…”

Section: Trout Il-15 (+Sil-15rα) Induces Expression Of Type 1 Immunity Marker Genes In Trout Total Splenocytes But Trout Il-15l+sil-15rα mentioning

confidence: 99%

“…IL-2 and IL-15 signal through the heterodimer type I receptor IL-2Rβ•IL-2Rγ and can induce very similar transcription profiles (16). Both IL-2 and IL-15 activate the transcription factor STAT5 (15,17). Whereas, free IL-2 and IL-15 molecules can bind with low efficiency to IL-2Rβ•IL-2Rγ heterodimers, the cytokine-specific and efficient receptor complexes are formed by the heterotrimers IL-2Rα•IL-2Rβ•IL-2Rγ and IL-15Rα•IL-2Rβ•IL-2Rγ, respectively (16,(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

et al. 2020

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Related interleukin-2, -15, and -15-like (IL-2, -15, and -15L) are ancient cytokines, with all three genes surviving in extant fish and some mammals. The present study is the first to identify IL-15L functions, namely in rainbow trout. In isolated trout splenocytes, and in vivo, purified recombinant IL-15L+IL-15Rα molecules induced expression of IL-4 and IL-13 homologs, which are markers of type 2 immunity. In contrast, trout IL-15 stimulated type 1 immunity markers, thus IL-15 and IL-15L can have opposing functions. Trout IL-15L was more dependent on "in trans" presentation by the receptor chain IL-15Rα than IL-15, and stimulated CD4 − CD8 − (IgM − ) lymphocytes from thymus and spleen. We propose an important role for IL-15L early in the type 2 immunity cytokine cascade. Trout IL-2 and IL-15 exhibited features reminiscent of their mechanistic and functional dichotomy observed in mammals; for example, IL-15 but not IL-2 required a receptor alpha chain (only IL-15Rα in the case of fish) for its stability, and only IL-15 was efficient in stimulating lymphocytes from mucosal tissues. Data suggest that IL-15L and IL-15 may be particularly effective in stimulating innate lymphocyte type 2 cells (ILC2) and natural killer (NK) cells, respectively, but further identification of the cell types is needed. An interesting finding different from in mammals was the efficient stimulation of CD4 + CD8 + thymocytes by IL-2. In short, this study presents fundamental information on the evolution of the IL-2/15/15L cytokine family.

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Section: Trout Il-15 (+Sil-15rα) Induces Expression Of Type 1 Immunity Marker Genes In Trout Total Splenocytes But Trout Il-15l+sil-15rα mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

et al. 2020

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“…Phosphorylation of STAT5 and STAT3 by JAK1 and JAK3 causes the STAT molecules to homodimerize or heterodimerize and translocate to the nucleus (Johnston et al, 1995). Although both STAT5 and STAT3 are activated by IL-2R signaling, STAT3 is activated to a lesser degree than STAT5 (Delespine-Carmagnat et al, 2000). STAT5 activation promotes T lymphocyte proliferation and transcription of various genes involved in cell cycle progression (e.g., c-myc,cyclin D2) and cell survival (e.g., bcl-2 and bcl-x) .…”

Section: Introductionmentioning

confidence: 99%

Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways

et al. 2015

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“…in pro-B cells [14], primary human T and NK cells [13], HPB T lymphoblasts [23], CT6 cells [8], as well as in EK293T, CHO and COS-7 cells [24]. For Kit 225 cells, STAT5 phosphorylation has already been shown by IL-2 activation [25,26], [27]. However, to our knowledge, IL-7 induced phosphorylation in Kit 225 cells has not yet been reported so far.…”

Section: Stat5 Western Blot Analysismentioning

confidence: 95%

Development of a STAT5 Phosphorylation Assay as a Rapid Bioassay to Assess Interleukin-7 Potency

Zumpe

Engel²,

Wiedemann³

et al. 2011

CPB

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Interleukin (IL)-7 is a cytokine inducing the Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway. As a consequence of IL-7 activating this pathway, STAT5 is phosphorylated. In pharmaceutical quality control, the potency of biopharmaceuticals is commonly assessed by proliferation assays. This is also possible for IL-7 conjugates. However, the disadvantage of these classical "endpoint-assays" is that they require very long incubation times, up to several days, since they measure the downstream events of a cellular response. As an alternative to this, we developed a rapid intracellular phosphorylation assay, measuring IL-7 induced STAT5 phosphorylation in Kit 225 cells. The Kit 225 human T cell line expresses the IL-7 receptor and is responsive to IL-7, therefore making it a good candidate cell line for assay development. Like the Kinase receptor activation (KIRA) assay, developed by Sadick et al. [1], the STAT5 phosphorylation assay was performed using two separate microtiter plates: the first one for cell stimulation and lysis, the second one for enzyme-linked immuno sorbent assay (ELISA). The assay showed a high accuracy and precision with a mean recovery of 102% and a mean coefficient of variation of 9%. In comparison to the classical proliferation assay, the phosphorylation assay is much faster. Thus, the assay procedure time can at least be reduced from six to three days by using STAT5 phosphorylation instead of proliferation as an endpoint due to the shorter incubation time with IL-7. Moreover, the phosphorylation assay shows a wider dynamic range and higher signal to noise ratios and is thus more robust than the proliferation assay.mAs a consequence, this assay could serve as reliable, accurate, precise and fast alternative to the classical proliferation assay for IL-7. This study also serves as an example for the typical steps during development and qualification / validation of a potency assay for quality control testing.

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Association of STAT1, STAT3 and STAT5 proteins with the IL-2 receptor involves different subdomains of the IL-2 receptor β chain

Cited by 39 publications

References 37 publications

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways

Development of a STAT5 Phosphorylation Assay as a Rapid Bioassay to Assess Interleukin-7 Potency

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