IL-3-Induced Immediate Expression of c-<i>fos</i> and c-<i>jun</i> Is Modulated by the IKK2-JNK Axis
Interleukin (IL)-3 is a pleiotropic cytokine that regulates the survival, proliferation, and differentiation of hematopoietic cells. The binding of IL-3 to its receptor activates intracellular signaling, inducing transcription of immediate early genes (IEGs) such as c-<i>fos</i>, c-<i...
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MDPI AG
2022-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/9/1451 |
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| author | Hirotaka Fujita Toshitsugu Fujita Hodaka Fujii |
| author_facet | Hirotaka Fujita Toshitsugu Fujita Hodaka Fujii |
| author_sort | Hirotaka Fujita |
| collection | DOAJ |
| description | Interleukin (IL)-3 is a pleiotropic cytokine that regulates the survival, proliferation, and differentiation of hematopoietic cells. The binding of IL-3 to its receptor activates intracellular signaling, inducing transcription of immediate early genes (IEGs) such as c-<i>fos</i>, c-<i>jun</i>, and c-<i>myc</i>; however, transcriptional regulation under IL-3 signaling is not fully understood. This study assessed the role of the inhibitor of nuclear factor-κB kinases (IKKs) in inducing IL-3-mediated expression of IEGs. We show that IKK1 and IKK2 are required for the IL-3-induced immediate expression of c-<i>fos</i> and c-<i>jun</i> in murine hematopoietic Ba/F3 cells. Although IKK2 is well-known for its pivotal role as a regulator of the canonical nuclear factor-κB (NF-κB) pathway, activation of IKKs did not induce the nuclear translocation of the NF-κB transcription factor. We further revealed the important role of IKK2 in the activation of c-Jun N-terminal kinase (JNK), which mediates the IL-3-induced expression of c-<i>fos</i> and c-<i>jun</i>. These findings indicate that the IKK2-JNK axis modulates the IL-3-induced expression of IEGs in a canonical NF-κB-independent manner. |
| first_indexed | 2024-03-10T04:17:16Z |
| format | Article |
| id | doaj.art-af77d8cab2014d4a8f21f5b6e9b194ab |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:17:16Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-af77d8cab2014d4a8f21f5b6e9b194ab2023-11-23T07:59:25ZengMDPI AGCells2073-44092022-04-01119145110.3390/cells11091451IL-3-Induced Immediate Expression of c-<i>fos</i> and c-<i>jun</i> Is Modulated by the IKK2-JNK AxisHirotaka Fujita0Toshitsugu Fujita1Hodaka Fujii2Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Aomori, JapanDepartment of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Aomori, JapanDepartment of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Aomori, JapanInterleukin (IL)-3 is a pleiotropic cytokine that regulates the survival, proliferation, and differentiation of hematopoietic cells. The binding of IL-3 to its receptor activates intracellular signaling, inducing transcription of immediate early genes (IEGs) such as c-<i>fos</i>, c-<i>jun</i>, and c-<i>myc</i>; however, transcriptional regulation under IL-3 signaling is not fully understood. This study assessed the role of the inhibitor of nuclear factor-κB kinases (IKKs) in inducing IL-3-mediated expression of IEGs. We show that IKK1 and IKK2 are required for the IL-3-induced immediate expression of c-<i>fos</i> and c-<i>jun</i> in murine hematopoietic Ba/F3 cells. Although IKK2 is well-known for its pivotal role as a regulator of the canonical nuclear factor-κB (NF-κB) pathway, activation of IKKs did not induce the nuclear translocation of the NF-κB transcription factor. We further revealed the important role of IKK2 in the activation of c-Jun N-terminal kinase (JNK), which mediates the IL-3-induced expression of c-<i>fos</i> and c-<i>jun</i>. These findings indicate that the IKK2-JNK axis modulates the IL-3-induced expression of IEGs in a canonical NF-κB-independent manner.https://www.mdpi.com/2073-4409/11/9/1451IL-3IKKimmediate early geneJNK |
| spellingShingle | Hirotaka Fujita Toshitsugu Fujita Hodaka Fujii IL-3-Induced Immediate Expression of c-<i>fos</i> and c-<i>jun</i> Is Modulated by the IKK2-JNK Axis Cells IL-3 IKK immediate early gene JNK |
| title | IL-3-Induced Immediate Expression of c-<i>fos</i> and c-<i>jun</i> Is Modulated by the IKK2-JNK Axis |
| title_full | IL-3-Induced Immediate Expression of c-<i>fos</i> and c-<i>jun</i> Is Modulated by the IKK2-JNK Axis |
| title_fullStr | IL-3-Induced Immediate Expression of c-<i>fos</i> and c-<i>jun</i> Is Modulated by the IKK2-JNK Axis |
| title_full_unstemmed | IL-3-Induced Immediate Expression of c-<i>fos</i> and c-<i>jun</i> Is Modulated by the IKK2-JNK Axis |
| title_short | IL-3-Induced Immediate Expression of c-<i>fos</i> and c-<i>jun</i> Is Modulated by the IKK2-JNK Axis |
| title_sort | il 3 induced immediate expression of c i fos i and c i jun i is modulated by the ikk2 jnk axis |
| topic | IL-3 IKK immediate early gene JNK |
| url | https://www.mdpi.com/2073-4409/11/9/1451 |
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