期刊
JOURNAL OF IMMUNOLOGY
卷 165, 期 5, 页码 2556-2562出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.165.5.2556
关键词
-
类别
资金
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R56AI040114, R01AI040114] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI40114] Funding Source: Medline
The common gamma -chain (gammac), a subunit of the IL-2R, is essential for high affinity ligand binding and signal transduction due to Jak3 association to gammac, Another consequence of IL-2/IL-2R interaction is rapid receptor-mediated endocytosis of the receptor-ligand complex. In the present study, we establish that this rapid endocytosis of IL-2 in a T cell tumor line is dependent upon the cytoplasmic tail of gammac, Deletion mutants of the cytoplasmic tail mapped this activity to 9 aa of gammac, 45-54 aa distal to the transmembrane region. In contrast, ligand-independent constitutive endocytosis of gammac occurred more slowly and was dependent upon a PEST sequence in a more membrane-proximal region of the cytoplasmic tail of gammac, Thus, this receptor subunit may use distinct sorting signals for its constitutive regulation and ligand-induced endocytosis. Rapid endocytosis of IL-2 was inhibited by the tyrosine kinase inhibitor genistein, implicating a role for a signal transduction pathway in IL-2 internalization. However, one T cell line bearing a mutant gammac exhibited impaired endocytosis of IL-2, despite normal IL-2-induced Jak/STAT activation, Furthermore, inefficient endocytosis of IL-2 was noted after transfection of the COS7 epithelial cell line with the IL-2R, and further reconstitution of these cells with Jak/STAT proteins did not enhance this internalization. Collectively, these latter findings indicate that rapid endocytosis of IL-2 is dependent upon cellular signaling in lymphoid cell environment that is not solely a consequence of the presence of the Jak/STAT pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据