Cloning of a T Cell Growth Factor that Interacts with the β Chain of the Interleukin-2 Receptor

Grabstein, Kenneth H.; Eisenman, June; Shanebeck, Kurt; Rauch, Charles T.; Srinivasan, Subhashini; Fung, Victor; Beers, Courtney; Richardson, Jane S.; Schoenborn, Michael A.; Ahdieh, Minoo; Johnson, Leslie D.; Alderson, Mark R.; Watson, James D.; Anderson, D; Giri, Judith G.

doi:10.1126/science.8178155

Cited by 1,357 publications

(1,178 citation statements)

References 24 publications

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“…IL-15 was ®rst characterized for its ability to stimulate the proliferation of the murine IL-2-dependent lymphoid cell line CTLL2. It was subsequently shown that IL-15 mimics many other functional properties of IL-2, including stimulation of LAK activity, GM-CSF and IFNg secretion by NK cells as well as proliferation of T, B, and NK cells (Bamford et al, 1994;Grabstein et al, 1994;Carson et al, 1994Carson et al, , 1996Armitage et al, 1995;Gamero et al, 1995). Despite these overlapping activities IL-15 does not share sequence homology with IL-2, even if both cytokines belong to the four a helices cytokine and share the b and g receptor subunits .…”

Section: Introductionmentioning

confidence: 99%

IL-15 is produced by a subset of human melanomas, and is involved in the regulation of markers of melanoma progression through juxtacrine loops

Barzegar

Meazza²,

Pereno

et al. 1998

Oncogene

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Section: Introductionmentioning

confidence: 99%

IL-15 is produced by a subset of human melanomas, and is involved in the regulation of markers of melanoma progression through juxtacrine loops

Barzegar

Meazza²,

Pereno

et al. 1998

Oncogene

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“…Both cytokines are therefore mutually exclusive in their production in various cell types [34]. Even though their amino acid sequence shows no homology [34,36], the biological action of both proteins seems to be similar as activators of CD4 + and CD8 + T lymphocytes, gd T cells, NK cells and B lymphocytes [40][41][42][43][44][45][46]. This could be explained by the observation that both IL-2 and IL-15 bind to the IL-2R b-and g cchain [34,36].…”

Section: Introductionmentioning

confidence: 99%

“…Even though their amino acid sequence shows no homology [34,36], the biological action of both proteins seems to be similar as activators of CD4 + and CD8 + T lymphocytes, gd T cells, NK cells and B lymphocytes [40][41][42][43][44][45][46]. This could be explained by the observation that both IL-2 and IL-15 bind to the IL-2R b-and g cchain [34,36]. Binding affinity of both cytokines to the IL-2R subunits and the number of high affinity receptors on activated human peripheral blood mononuclear cells (PBMC) seems to be similar as well [34].…”

Section: Introductionmentioning

confidence: 99%

“…This could be explained by the observation that both IL-2 and IL-15 bind to the IL-2R b-and g cchain [34,36]. Binding affinity of both cytokines to the IL-2R subunits and the number of high affinity receptors on activated human peripheral blood mononuclear cells (PBMC) seems to be similar as well [34]. Instead of the IL-2R a-chain IL-15 seems to utilize a binding protein that is structurally related to, but different from, the IL-2R a-chain [47][48][49].…”

Section: Introductionmentioning

confidence: 99%

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Differential Role for IL‐2 and IL‐15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes

et al. 1997

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Lorenz H-M, Hieronymus T, Grünke M, Manger B, Kalden JR. Differential Role for IL-2 and IL-15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes. Scand J Immunol 1997;45:660-669 Interleukin (IL)-15 is a newly described cytokine with properties similar to IL-2. Even though it does not share sequence homology with IL-2, both cytokines bind to the same receptor with the noted exception of a cytokine specific a-chain. In this study the authors compared IL-2 and IL-15 to determine their ability to rescue short term activated lymphocytes (phytohaemagglutinin stimulation of peripheral blood mononuclear cells for 6 days, followed by expansion in medium containing IL-2 for 2 days) from apoptotic cell death. The authors found that both IL-2 and IL-15 can inhibit induction of apoptosis in this experimental model with similar time and dose kinetics. On mRNA or protein levels induction of pro-and anti-apoptotic gene products like fasL, bcl-2, or bax with minor effects on fas/Apo-1 or bcl-x L was observed under culture conditions with both IL-2 and IL-15. Next, it was found that phytohaemagglutinin (PHA) blasts were less responsive (in terms of cellular proliferation and prevention from apoptosis) to IL-2 if signals through the a-chain were blocked, with no effect on b-chain specific monoclonal antibodies (MoAb). By contrast, IL-15 was less effective in induction of cellular proliferation and prevention of apoptosis if IL-2R b-chain specific MoAb were added to cell cultures. Testing intracellular signalling induced by IL-2 or IL-15, the authors found identical changes in tyrosine phosphorylation patterns in PHA blasts cultured in medium or under IL-2 or IL-15 stimulation. By contrast, they found consistent differences if PHA stimulated peripheral blood mononuclear cells (PBMC) were expanded in medium containing IL-15 (instead of IL-2). These IL-15 expanded PHA blasts showed a significantly increased percentage of apoptosis after growth factor withdrawal. Furthermore, IL-2 was more efficient than IL-15 in rescuing IL-15 expanded PHA blasts from apoptosis. In IL-15 expanded PHA blasts expression of IL-2R a-chain was lower than that in IL-2 expanded PHA blasts. A model presenting a differential role for IL-2 and IL-15 in inhibition of apoptosis in vivo is discussed.

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“…IL-15 was initially identified as a cytokine that could support the proliferation of an IL-2 dependent cell line in the presence of neutralizing antibodies against IL-2 [103,104]. Some similarities in the in vitro activities of IL-2 and IL-15 are mediated by a shared receptor subunit [105]; however studies in mice lacking IL-15 [106] or IL-2 [107] suggest that the two cytokines mediate distinct biological functions [108].…”

Section: Rantesmentioning

confidence: 99%

Mnk kinases in cytokine signaling and regulation of cytokine responses

Joshi¹,

Platanias²

2012

Biomolecular Concepts

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The kinases Mnk1 and Mnk2 are activated downstream of the p38 MAPK and MEK/ERK signaling pathways. Extensive work over the years has shown that these kinases control phosphorylation of the eukaryotic initiation factor 4E (eIF4E) and regulate engagement of other effector elements, including hnRNPA1 and PSF. Mnk kinases are ubiquitously expressed and play critical roles in signaling for various cytokine receptors, while there is emerging evidence that they have important functions as mediators of pro-inflammatory cytokine production. In this review the mechanisms of activation of MNK pathways by cytokine receptors are addressed and their roles in diverse cytokine-dependent biological processes are reviewed. The clinical-translational implications of such work and the relevance of future development of specific MNK inhibitors for the treatment of malignancies and auto-immune disorders are discussed.

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Cloning of a T Cell Growth Factor that Interacts with the β Chain of the Interleukin-2 Receptor

Cited by 1,357 publications

References 24 publications

IL-15 is produced by a subset of human melanomas, and is involved in the regulation of markers of melanoma progression through juxtacrine loops

IL-15 is produced by a subset of human melanomas, and is involved in the regulation of markers of melanoma progression through juxtacrine loops

Differential Role for IL‐2 and IL‐15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes

Mnk kinases in cytokine signaling and regulation of cytokine responses

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