Transactivation of erbB2 by short and long isoforms of leptin receptors.
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.
Eisenberg
Avital
A
Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel.
Biener
Eva
E
Charlier
Madia
M
Krishnan
R V
RV
Djiane
Jean
J
Herman
Brian
B
Gertler
Arieh
A
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins; D006801:Humans; D015151:Immunoblotting; D020738:Leptin / Q000737:chemistry; D008024:Ligands; D008164:Luminescent Proteins / Q000737:chemistry; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D054411:Receptors, Leptin; D011981:Receptors, Prolactin / Q000737:chemistry; D012756:Sheep; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection
D001426:Bacterial Proteins; D018076:DNA, Complementary; D049452:Green Fluorescent Proteins; D020738:Leptin; D008024:Ligands; D008164:Luminescent Proteins; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011981:Receptors, Prolactin; C515448:LEPR protein, human; C054562:yellow fluorescent protein, Bacteria