LIFR-BETA AND GP-130 AS HETERODIMERIZING SIGNAL TRANSDUCERS OF THE TRIPARTITE CNTF RECEPTOR

The ciliary neurotrophic factor (CNTF) receptor complex is shown here to include the CNTF binding protein (CNTFRalpha) as well as the compon ents of the leukemia inhibitory factor (LIF) receptor, LIFRbeta (the L IF binding protein) and gp130 [the signal transducer of interleukin-6 (IL-6)]. Thus, the conversion of a bipartite LIF receptor into a tripa rtite CNTF receptor apparently occurs by the addition of the specifici ty-conferring element CNTFRalpha. Both CNTF and LIF trigger the associ ation of initially separate receptor components, which in turn results in tyrosine phosphorylation of receptor subunits. Unlike the IL-6 rec eptor complex in which homodimerization of gp130 appears to be critica l for signal initiation, signaling by the CNTF and LIF receptor comple xes depends on the heterodimerization of gp130 with LIFRbeta. Ligand-i nduced dimerization of signal-transducing receptor components, also se en with receptor tyrosine kinases, may provide a general mechanism for the transmission of a signal across the cell membrane.