We report herein the characterization of activities of signal transduction for three types of leptin receptors (OBRs) from rats, the OBRa, OBRb, and OBRb with fa mutation (OBRb-fa), by measurement of the levels of tyrosine phosphorylation of STAT3 (signal transducers and activators of transcription 3) and MAPK (mitogen-activated protein kinase), which are induced by leptin stimulation of CHO cells stably expressing the OBR (CHO-OBRb, CHO-OBRa, or CHO-OBRb-fa cells). As the result of leptin stimulation, enhanced levels of tyrosine phosphorylation of STAT3 and MAPK were detected in CHO-OBRb cells. In CHO-OBRb-fa cells, enhancement levels for both were lower than those in CHO-OBRb cells. In CHO-OBRa cells, only the phosphorylation of MAPK was detected. These data suggest that these reduced signaling activities cause obesity in fa/fa rats and that OBRa, which has been generally thought to be inactive at signaling, actually transmits signals through the MAPK pathway. (C) 1998 Academic Press.