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J Immunol. 2000 Sep 1;165(5):2556-62.

Efficient internalization of IL-2 depends on the distal portion of the cytoplasmic tail of the IL-2R common gamma-chain and a lymphoid cell environment.

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Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136, USA.


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.

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