Modulation of Interleukin (IL)-13 Binding and Signaling by the γc Chain of the IL-2 Receptor

Abstract

Interleukin-13 (IL-13)1 and IL-4 are pleiotropic immune regulatory cytokines, which are predominantly produced by activated lymphocytes. Both cytokines mediate similar effects on B cells and monocytes; however, IL-13 has not been shown to have direct effects on T cells (1-3). The effects of both cytokines are mediated by cell surface receptors (R) that are specific for each of these ligands (4, 5). The receptor for IL-4 has been extensively investigated and its structure appears to vary with cell types. We have proposed three models for the structure of the IL-4R complex (6). However, despite their structural differences, all of the identified forms of the IL-4R complex are quite effective in transducing signals in response to IL-4 binding.Unlike the IL-4 receptor system, the receptor for IL-13 has not been well characterized. We have demonstrated that RCC cells express a large number of IL-13 binding sites and that these cells respond to IL-13 (4, 7). Cross-linking studies indicate that the IL-13R is predominantly composed of a ϳ65-70-kDa protein (4). RCC cells also express IL-4R, and 125

Unusual interleukin-4 and -13 signaling in human normal and tumor lung fibroblasts

“…Finally in lung myo®broblasts, the constitutive expression of the gc chain, does not interfere with IL-4 or IL-13 binding (Doucet et al, 1998a) nor JAK/ STAT signaling; but favors JAK3 phosphorylation, in contrast to what has been shown previously in renal carcinoma cells transfected with the gc chain (Obiri et al, 1997).…”

“…Moreover, the constitutive expression of the gc chain in human lung tumor myo®broblasts does not inhibit the JAK/STAT signaling pathways in response to IL-4 and IL-13 as suggested elsewhere (Obiri et al, 1997), but in addition partially modify the pattern of JAKs activation in this type of cell.…”

Mutants of Interleukin 13 with Altered Reactivity toward Interleukin 13 Receptors

“…hIL13 does not bind the p140 subunit of the shared receptor complex in the absence of ␣Ј, contrary to the ability of hIL4 to interact with it (17). Although hIL13 and hIL4 use this shared receptor on some normal cells (18) and on some adenocarcinomas (19), several other malignant cells, such as human malignant gliomas, express an abundance of a hIL13 receptor that is not shared with hIL4 (20,21). In addition, a protein has been currently identified that binds hIL13 avidly, with no affinity toward hIL4 (22), but its role as a glioma-associated receptor for hIL13 remains to be demonstrated.…”

Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors engineered to express IL-13 receptor α2 chain in vivo

“…[7][8][9] We have shown that the receptor for IL-13 (IL-13R) in tumor cells exists as two different types. [10][11][12][13][14][15] Type I IL-13R consists of IL-13Ra2 (also known as IL-13Ra), IL-13Ra1 (also known as IL-13Ra 0 ), and IL-4Ra (also known as IL-4Rb) chains, while type II IL-13R consists of IL-13Ra1 and IL-4Ra chains. IL-13Ra1 chain [16][17][18] forms a heterodimer with IL4Ra chain and this complex mediates signal transduction through the JAK-STAT pathway.…”