Journal of Biological Chemistry
Volume 272, Issue 32, 8 August 1997, Pages 19982-19986
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NUCLEIC ACIDS, PROTEIN SYNTHESIS, AND MOLECULAR GENETICS
Distinct Roles for Leukemia Inhibitory Factor Receptor α-Chain and gp130 in Cell Type-specific Signal Transduction*

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Leukemia inhibitory factor (LIF) induces a variety of disparate biological responses in different cell types. These responses are thought to be mediated through the functional LIF receptor (LIFR), consisting of a heterodimeric complex of LIFR α-chain (LIFRα) and gp130. The present study investigated the relative capacity of the cytoplasmic domains of each receptor subunit to signal particular responses in several cell types. To monitor the signaling potential of LIFRα and gp130 individually, we constructed chimeric receptors by linking the extracellular domain of granulocyte colony-stimulating factor receptor (GCSFR) to the transmembrane and cytoplasmic regions of either LIFRα or gp130. Both chimeric receptors and the full-length GCSFR in expressed in M1 myeloid leukemic cells to measure differentiation induction, in embryonic stem cells to measure differentiation inhibition, and in Ba/F3 cells to measure cell proliferation. Our results demonstrated that whereas GCSFR-gp130 receptor homodimer mediated a GCSF-induced signal in all three cell types, the GCSFR-LIFRα receptor homodimer was only functional in embryonic stem cells. These findings suggest that the signaling potential of gp130 and LIFRα cytoplasmic domains may differ depending upon the tissue and cellular response initiated.

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*

This work was supported by the Anti-Cancer Council of Victoria, Melbourne, Australia; AMRAD Operations Pty. Ltd., Melbourne, Australia; the National Health and Medical Research Council, Canberra, Australia; the J. D. and L. Harris Trust; National Institutes of Health Grant Grant CA-22556; and the Australian Federal Government Cooperative Research Centres Program.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by a Queen Elizabeth II Postdoctoral Fellowship from the Australian Research Council.