LIFRβ 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 (CNTFR[Alpha]) as well as the components of the leukemia inhibitory factor (LIF) receptor, LIFR[Beta] (the LIF binding protein) and gp 130 [the signal transducer of interleukin-6 (IL-6)]. Thus, the conversion of a bipartite LIF receptor into a tripartite CNTF receptor apparently occurs by the addition of the specificity-conferring element CNTFR[Alpha]. Both CNTF and LIF trigger the association of initially separate receptor components, which in turn results in tyrosine phosphorylation of receptor subunits. Unlike the IL-6 receptor complex in which homodimerization of gp 130 appears to be critical for signal initiation, signaling by the CNTF and LIF receptor complexes depends on the heterodimerization of gp 130 with LIFR[Beta]. Ligand-induced dimerization of signal-transducing receptor components, also seen with receptor tyrosine kinases, may provide a general mechanism for the transmission of a signal across the cell membrane.