Title: ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner
Authors : Olayioye, Monilola A.
Graus-Porta, Diana
Beerli, Roger R.
Rohrer, Jack
Gay, Brigitte
Hynes, Nancy E.
Published in : Molecular and Cellular Biology
Volume(Issue) : 18
Issue : 9
Pages : 5042
Pages to: 5051
Publisher / Ed. Institution : American Society for Microbiology
Issue Date: Sep-1998
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subject (DDC) : 571: Physiology and related subjects
572: Biochemistry
Abstract: The different epidermal growth factor (EGF)-related peptides elicit a diverse array of biological responses as the result of their ability to activate distinct subsets of ErbB receptor dimers, leading to the recruitment of different intracellular signalling networks. To specifically examine dimerization-dependent modulation of receptor signalling, we constructed NIH 3T3 cell lines expressing ErbB-1 and ErbB-2 singly and in pairwise combinations with each other ErbB family member. This model system allowed the comparison of EGF-activated ErbB-1 with ErbB-1 activated by Neu differentiation factor (NDF)-induced heterodimerization with ErbB-4. In both cases, ErbB-1 coupled to the adaptor protein Shc, but only when activated by EGF was it able to interact with Grb2. Compared to the rapid internalization of EGF-activated ErbB-1, NDF-activated ErbB-1 showed delayed internalization characteristics. Furthermore, the p85 subunit of phosphatidylinositol kinase (PI3-K) associated with EGF-activated ErbB-1 in a biphasic manner, whereas association with ErbB-1 transactivated by ErbB-4 was monophasic. The signalling properties of ErbB-2 following heterodimerization with the other ErbB receptors or homodimerization induced by point mutation or monoclonal antibody treatment were also analyzed. ErbB-2 binding to peptides containing the Src homology 2 domain of Grb2 or p85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation. Finally, tryptic phosphopeptide mapping of both ErbB-1 and ErbB-2 revealed that receptor phosphorylation is dependent on the dimerization partner. Differential receptor phosphorylation may, therefore, be the basis for the differences in the signalling properties observed.
Departement: Life Sciences und Facility Management
Publication type: Article in scientific Journal
DOI : 10.1128/MCB.18.9.5042
ISSN: 0270-7306
URI: https://digitalcollection.zhaw.ch/handle/11475/6818
Appears in Collections:Publikationen Life Sciences und Facility Management

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