Overlapping and distinct signals through leptin receptor (OB-R) and a closely related cytokine signal transducer, gp130

The structure of leptin receptor (OB-R) is highly homologous to that of gp130, the common signal transducing receptor component for the interleukin-6 family of cytokines, Based on this structural similarity, we examined signaling processes initiated by OB-R in comparison with those by gp130, Stimulation of either a long form of OB-R or gp130 led to tyrosine phosphorylation of STAT3, whereas stimulation of the truncated form of OB-R that is predominantly expressed in db/db mice failed to do so, Stimulation of the long form OB-R did not induce tyrosine phosphorylation of a Src homology domain 2 containing protein tyrosine phosphatase, SHP-2, while stimulation of gp130 did, In contrast, activation of p42(ERK2) is mediated by either the long form OB-R or gp130. Two closely related molecules, OB-R and gp130, thus appear to mediate overlapping but distinct signaling procedures.