We generated kinase-positive and kinase-negative erbB2 tagged with YFP and the long form of leptin receptor (LEPRb) tagged with CFP. Both were as active as their untagged analogs. Both short and long isoforms of leptin receptor phosphorylated and thereby activated erbB2 upon leptin binding and enhanced MAPK activity. Our results unveil a novel route by which leptin may provoke erbB2's phosphorylation and thus enhance its oncogenic potential independently of HER family ligands or its overexpression. Using FRET technology in living cells, we found no evidence of complex formation between erbB2 and prolactin or leptin receptors, indicating that the transactivation occurs through an indirect interaction.
Bibliographical noteFunding Information:
This work was supported by the Binational USA – Israel Science Foundation (Grant No. 2000115) to AG and BH. We thank Dr. Y. Yarden from the Weizmann Institute, Rehovot, Israel for the plasmids encoding erbB2 and KN erbB2 and reading this manuscript, Dr. C. Bjorbaek from Harvard Medical School, Boston, MA for the plasmids encoding mouse LEPRs and Ms. Nathalie Daniel for the help in bioassay of LEPRb-CFP.
- Fluorescence resonance energy transfer