title: Suppressor of Cytokine Signaling 2 Negatively Regulates NK Cell Differentiation by Inhibiting JAK2 Activity.
abstract: Suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine responses. Although recent reports have shown regulatory roles for SOCS proteins in innate and adaptive immunity, their roles in natural killer (NK) cell development are largely unknown. Here, we show that SOCS2 is involved in NK cell development. SOCS2-/-mice showed a high frequency of NK cells in the bone marrow and spleen. Knockdown of SOCS2 was associated with enhanced differentiation of NK cells in vitro, and the transplantation of hematopoietic stem cells (HSCs) into congenic mice resulted in enhanced differentiation in SOCS2-/-HSCs. We found that SOCS2 could inhibit Janus kinase 2 (JAK2) activity and JAK2-STAT5 signaling pathways via direct interaction with JAK2. Furthermore, SOCS2-/-mice showed a reduction in lung metastases and an increase in survival following melanoma challenge. Overall, our findings suggest that SOCS2 negatively regulates the development of NK cells by inhibiting JAK2 activity via direct interaction.
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Won Sam
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Dong Oh
authors.initials: DO
authors.lastname: Kim
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Biochemistry, School of Life Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea.
authors.forename: Jae-Eun
authors.initials: JE
authors.lastname: Byun
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Hangsak
authors.initials: H
authors.lastname: Huy
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Song
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Haiyoung
authors.initials: H
authors.lastname: Jung
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D050799:STAT5 Transcription Factor / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019409:Interleukin-15; D050799:STAT5 Transcription Factor; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2