ArticlePloS one2013
A fusion cytokine coupling GMCSF to IL9 induces heterologous receptor clustering and STAT1 hyperactivation through JAK2 promiscuity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- An autologous cell-based therapeutic vaccine expressing IL6/1 fusokine drives robust anti-tumor response against ovarian cancer.bioRxiv : the preprint server for biology · 2026Article
- Cytokine receptor clustering in sensory neurons with an engineered cytokine fusion protein triggers unique pain resolution pathways.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- HCV and flaviviruses hijack cellular mechanisms for nuclear STAT2 degradation: Up-regulation of PDLIM2 suppresses the innate immune response.PLoS pathogens · 2019Article
- JAK2V617F but not CALR mutations confer increased molecular responses to interferon-α via JAK1/STAT1 activation.Leukemia · 2019Article
- Evolution of the magic bullet: Single chain antibody fragments for the targeted delivery of immunomodulatory proteins.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- GIFT4 fusokine converts leukemic B cells into immune helper cells.Journal of translational medicine · 2016Article
- A GMCSF and IL7 fusion cytokine leads to functional thymic-dependent T-cell regeneration in age-associated immune deficiency.Clinical & translational immunology · 2015Article
- Concise review: engineering the fusion of cytokines for the modulation of immune cellular responses in cancer and autoimmune disorders.Stem cells translational medicine · 2015Review
- Engineered fusokine GIFT4 licenses the ability of B cells to trigger a tumoricidal T-cell response.Cancer research · 2014Article
- Maltose-binding protein fusion allows for high level bacterial expression and purification of bioactive mammalian cytokine derivatives.PloS one · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cytokine receptors are randomly distributed on the cell surface membrane and are activated upon binding of their extracellular ligands to mediate downstream cellular activities. We hypothesized that pharmaceutical clustering of ligand-bound, activated receptors may lead to heretofore unrealized gain-of-function with therapeutically desirable properties. We here describe an engineered bifunctional cytokine borne of the fusion of Granulocyte Macrophage Colony Stimulating Factor (GMCSF) and Interleukin-9 (IL9) (hereafter GIFT9 fusokine) and demonstrate that it chaperones co-clustering of the functionally unrelated GMCSF receptor (GMCSFR) and IL9 receptor (IL9R) on cell surface of target cells. We demonstrate that GIFT9 treatment of MC/9 cells leads to transhyperphosphorylation of IL9R-associated STAT1 by GMCSFR-associated JAK2. We also show that IL9R-associated JAK1 and JAK3 augment phosphorylation of GMCSFR-linked STAT5. The functional relevance of these synergistic JAK/STAT transphosphorylation events translates to an increased mitogenic response by GMCSFR/IL9R-expressing primary marrow mast cells. The notion of inducing heterologous receptor clustering by engineered fusokines such as GIFT9 opens the door to a novel type of biopharmaceutical platform where designer fusokines modulate cell physiology through clustering of targeted receptor complexes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.