Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal transduction
Starr, R; Novak, U; Willson, TA; Inglese, M; Murphy, V; Alexander, WS; Metcalf, D; Nicola, NA; Hilton, DJ; Ernst, M
JOURNAL OF BIOLOGICAL CHEMISTRY
Leukemia inhibitory factor (LIF) induces a variety of disparate biological responses ill different cell types. These responses are thought to be mediated through the functional LIF receptor (LIFR), consisting of a heterodimeric complex of LIFE alpha-chain (LIFR alpha) 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 LIFR alpha 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 LIFR alpha or gp130, Both chimeric receptors and the fall-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-LIFR alpha receptor homodimer was only functional in embryonic stem cells, These findings suggest that the signaling potential of gp130 and LIFR alpha cytoplasmic domains may differ depending upon the tissue and cellular response initiated.