Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL-5RA intracellular signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL
文献类型：期刊论文
| 作者 | Li, Bin4,5,6; Li, Cui4; Peng, Zhenzi4; Wang, Jun4; Dong, Yeping4; Zhang, Chunfang4; Duan, Chaojun4; Zhang, Guangsen5; Li, Ruijuan5; Lu, Jingchen6 |
| 刊名 | ONCOTARGET
 |
| 出版日期 | 2017 |
| 卷号 | 8期号:39页码:64984-64998 |
| ISSN号 | 1949-2553 |
| 关键词 | Lyn CEL |
| DOI | 10.18632/oncotarget.11401 |
| 文献子类 | Article |
| 英文摘要 | The Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) oncogene can cause chronic eosinophilic leukemia (CEL), but requires IL-5 cytokine participation. In this study, we investigate the mechanism of F/P in collaboration with IL-5 in CEL. The results showed that Lyn, a key effector in the IL-5-motivated eosinophil production, is extensively activated in F/P-positive CEL cells. Lyn can associate and phosphorylate IL-5 receptor a (IL-5RA) in F/P-positive cells. Moreover, the activation of Lyn and IL-5R kinase were strengthened when the cells were stimulated by IL-5. Lyn inhibition in F/P-positive CEL cells attenuated cellular proliferation, induced apoptosis, and blocked cell migration and major basic protein (MBP) release. We identified the FIP1L1-PDGFRA/JAK2/Lyn/Akt complex in the F/P-expressing cells which can be disrupted by dual inhibition of JAK2 and Lyn, repressing cell proliferation in both EOL-1(F/P-positive human eosinophilic cell line) and imatinib-resistance (IR) cells. Altogether, our data demonstrate that Lyn is a vital downstream kinase activated by F/P converged with IL-5 signals in CEL cells. Lyn activate and expand IL-5RA intracellular signaling through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex, provoking eosinophils proliferation and exaggerated activation manifested as CEL. |
| 学科主题 | Oncology ; Cell Biology |
| WOS关键词 | HUMAN EOSINOPHILS ; HYPEREOSINOPHILIC SYNDROME ; TYROSINE KINASE ; SYSTEMIC MASTOCYTOSIS ; MURINE MODEL ; PDGFR-ALPHA ; IN-VITRO ; LEUKEMIA ; ACTIVATION ; RECEPTOR |
| 语种 | 英语 |
| 出版者 | IMPACT JOURNALS LLC |
| WOS记录号 | WOS:000410291200025 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/760]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA; 2.Shanghai Jiao Tong Univ, Sch Med, Chinese Acad Sci, Inst Hlth Sci,Shanghai Inst Biol Sci, Shanghai, Peoples R China, 3.Harvard Med Sch, Boston, MA USA; 4.Cent S Univ, Xiangya Hosp, Chinese Minist Hlth, Med Res Ctr,Key Lab Canc Prote, Changsha, Hunan, Peoples R China; 5.Cent S Univ, Xiang Ya Hosp 2, Inst Mol Hematol, Div Hematol, Changsha, Hunan, Peoples R China; 6.Cent S Univ, Xiangya Hosp, Div Oncol, Changsha, Hunan, Peoples R China; 7.Cent S Univ, Xiangya Med Sch, State Key Lab Med Genet, Changsha, Hunan, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Bin,Li, Cui,Peng, Zhenzi,et al. Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL-5RA intracellular signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL[J]. ONCOTARGET,2017,8(39):64984-64998. |
| APA | Li, Bin.,Li, Cui.,Peng, Zhenzi.,Wang, Jun.,Dong, Yeping.,...&,.(2017).Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL-5RA intracellular signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL.ONCOTARGET,8(39),64984-64998. |
| MLA | Li, Bin,et al."Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL-5RA intracellular signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL".ONCOTARGET 8.39(2017):64984-64998. |
入库方式： OAI收割
来源：上海营养与健康研究所
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