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- Title
Extracellular domains drive homo- but not hetero-dimerization of erbB receptors.
- Authors
Ferguson, Kathryn M.; Darling, Paul J.; Mohan, Mohita J.; Macatee, Timothy L.; Lemmon, Mark A.
- Abstract
Many different growth factor ligands, including epidermal growth factor (EGF) and the neuregulins (NRGs), regulate members of the erbB/HER family of receptor tyrosine kinases. These growth factors induce erbB receptor oligomerization, and their biological specificity is thought to be defined by the combination of homo- and hetero-oligomers that they stabilize upon binding. One model proposed for ligand-induced erbB receptor hetero-oligomerization involves simple heterodimerization; another suggests that higher order hetero-oligomers are ‘nucleated’ by ligand-induced homodimers. To distinguish between these possibilities, we compared the abilities of EGF and NRG1-Β1 to induce homo- and hetero-oligomerization of purified erbB receptor extracellular domains. EGF and NRG1-Β1 induced efficient homo-oligomerization of the erbB1 and erbB4 extracellular domains, respectively. In contrast, ligand-induced erbB receptor extracellular domain hetero-oligomers did not form (except for s-erbB2-s-erbB4 hetero-oligomers). Our findings argue that erbB receptor extracellular domains do not recapitulate most heteromeric inter-actions of the erbB receptors, yet reproduce their ligand-induced homo-oligomerization properties very well. This suggests that mechanisms for homo- and hetero-oligomerization of erbB receptors are different, and contradicts the simple heterodimerization hypothesis prevailing in the literature.
- Subjects
EXTRACELLULAR matrix; LIGANDS (Biochemistry); EPIDERMAL growth factor; HER2 protein; PROTEIN-tyrosine kinases; CELL receptors
- Publication
EMBO Journal, 2000, Vol 19, Issue 17, p4632
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/19.17.4632