ErbB3/HER3 does not homodimerize upon neuregulin binding at the cell surface.
To understand signaling by the neuregulin (NRG) receptor ErbB3/HER3, it is important to know whether ErbB3 forms homodimers upon ligand binding. Previous biophysical studies suggest that the ErbB3 extracellular region remains monomeric when bound to NRG. We used a chimeric receptor approach to address this question in living cells, fusing the extracellular region of ErbB3 to the kinase-active intracellular domain of ErbB1. The ErbB3/ErbB1 chimera responded to NRG only if ErbB2 was co-expressed in the same cells, whereas an ErbB4/ErbB1 chimera responded without ErbB2. We, therefore, suggest that ErbB3 is an obligate heterodimerization partner because of its inability to homodimerize.
Berger
Mitchell B
MB
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6059, USA.
Mendrola
Jeannine M
JM
Lemmon
Mark A
MA
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane; D003001:Cloning, Molecular; D019281:Dimerization; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020880:Neuregulins / Q000378:metabolism*; D010766:Phosphorylation; D020893:Receptor, ErbB-3 / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018411:Spodoptera
D020880:Neuregulins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D066246:ErbB Receptors; D020893:Receptor, ErbB-3; D020928:Mitogen-Activated Protein Kinases