The upper cytokine-binding module and the Ig-like domain of the leukaemia inhibitory factor (LIF) receptor are sufficient for a functional LIF receptor complex 1 1Edited by M. Yaniv

Leukemia Inhibitory Factor (LIF), Cardiotrophin-1, and Oncostatin M Share Structural Binding Determinants in the Immunoglobulin-like Domain of LIF Receptor

“…The F284A mutation affected STAT3 phosphorylation in response to CT-1, but not to LIF or OSM. This is consistent with the larger EC 50 in proliferation required upon stimulation by CT-1 than by LIF (Fig. 4).…”

“…However, the effects of the D214A and/or F284A mutations in the LIFR Ig-like domains were similar to those observed with LIF. The D214A mutation did not induce any significant change in the proliferative response of the Ba/F3 cells induced by CT-1, whereas the F284A mutation markedly impaired cellular proliferation (100-fold increase in EC 50 ). The double mutation totally abrogated the proliferative response (at least 10,000-fold increase in EC 50 ).…”

“…LIF induced a robust proliferation of Ba/F3 cells expressing gp130 and wild type LIFR. Introducing the F284A mutation in LIFR impaired the proliferative response of Ba/F3 cells upon stimulation by LIF with a 10-fold increase in EC 50 ( Table I). The D214A mutation did not impair the proliferation of Ba/F3 cells and did not significantly alter EC 50 .…”

“…Introducing the F284A mutation in LIFR impaired the proliferative response of Ba/F3 cells upon stimulation by LIF with a 10-fold increase in EC 50 ( Table I). The D214A mutation did not impair the proliferation of Ba/F3 cells and did not significantly alter EC 50 . Unlike single mutations, which had no or moderate effects, the double mutation had a dramatic effect on Ba/F3 cell proliferation with an increase in EC 50 larger than 50,000-fold.…”

“…On the other hand, the double mutation impaired cell proliferation with a 20-fold increase in EC 50 (Table I). This indicates that OSM binds LIFR through the Ig-like domain.…”