Chimeric receptor analyses of the interactions of the ectodomains of ErbB-1 with epidermal growth factor and of those of ErbB-4 with neuregulin.
A series of chimeric receptors was generated between the epidermal growth factor (EGF) receptor, ErbB-1, and its homologue, ErbB-4, to investigate the roles of the extracellular domains (I-IV) in the ligand specificities. As compared with ErbB-1 and the chimeras with both domains I and III of ErbB-1, the chimeras with only one of these domains exhibited reduced binding of 125I-labeled EGF. Particularly, the contribution of domain III was appreciably larger than that of domain I of ErbB-1 in 125I-labeled EGF binding. Nevertheless, the chimeras with domain III of ErbB-1 and domain I of ErbB-4 were prevented from binding to 125I-labeled EGF competitively by the ErbB-4 ligand, neuregulin (NRG). On the other hand, NRG did not compete with 125I-labeled EGF for binding to the chimeras with the ErbB-1 domain I and the ErbB-4 domain III. Therefore, NRG binding to ErbB-4 depends much more on domain I than on domain III. With respect to autophosphorylation and subsequent ERK activation, EGF activated the chimeras with either domain I or III of ErbB-1. In contrast, NRG activated the chimeras with the ErbB-4 domain I and the ErbB-1 domain III, but not those with the ErbB-1 domain I and the ErbB-4 domain III. Therefore, the relative contributions between domains I and III of ErbB-4 in the NRG signaling are different from those of ErbB-1 in the EGF signaling.
Kim
Jae-Hoon
JH
Yokoyama CytoLogic Project, ERATO, Japan Science and Technology Corporation, c/o Tsukuba Research Consortium, Tokodai, Japan.
Saito
Kazuki
K
Yokoyama
Shigeyuki
S
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020880:Neuregulins / Q000378:metabolism*; D010766:Phosphorylation; D066247:Receptor, ErbB-4; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
D020880:Neuregulins; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D066247:Receptor, ErbB-4; D020928:Mitogen-Activated Protein Kinases