DISTINCT ROLES FOR LEUKEMIA INHIBITORY FACTOR-RECEPTOR ALPHA-CHAIN AND GP130 IN CELL-TYPE-SPECIFIC SIGNAL-TRANSDUCTION

Leukemia inhibitory factor (LIF) induces a variety of disparate biolog ical responses ill different cell types. These responses are thought t o be mediated through the functional LIF receptor (LIFR), consisting o f a heterodimeric complex of LIFE alpha-chain (LIFR alpha) and gp130. The present study investigated the relative capacity of the cytoplasmi c domains of each receptor subunit to signal particular responses in s everal cell types, To monitor the signaling potential of LIFR alpha an d gp130 individually, we constructed chimeric receptors by linking the extracellular domain of granulocyte colony-stimulating factor recepto r (GCSFR) to the transmembrane and cytoplasmic regions of either LIFR alpha or gp130, Both chimeric receptors and the fall-length GCSFR in e xpressed in M1 myeloid leukemic cells to measure differentiation induc tion, in embryonic stem cells to measure differentiation inhibition, a nd in Ba/F3 cells to measure cell proliferation. Our results demonstra ted that whereas GCSFR-gp130 receptor homodimer mediated a GCSF-induce d signal in all three cell types, the GCSFR-LIFR alpha receptor homodi mer was only functional in embryonic stem cells, These findings sugges t that the signaling potential of gp130 and LIFR alpha cytoplasmic dom ains may differ depending upon the tissue and cellular response initia ted.