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PMID: 1347745 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A subdomain in the transmembrane domain is necessary for p185neu* activation.

The EMBO journal ·Vol. 11 ·No. 3 ·1992-03-00 ·Pages 923-32

Cao H, Bangalore L, Bormann BJ, Stern DF

Abstract

The neu proto-oncogene encodes a protein highly homologous to the epidermal growth factor receptor. The neu protein (p185) has a molecular weight of 185,000 Daltons and, like the EGF receptor, possesses tyrosine kinase activity. neu is activated in chemically induced rat neuro/glioblastomas by substitution of valine 664 with glutamic acid within the transmembrane domain. The activated neu* protein (p185*) has an elevated tyrosine kinase activity and a higher propensity to dimerize, but the mechanism of this activation is still unknown. We have used site-directed mutagenesis to explore the role of specific amino acids within the transmembrane domain in this activation. We found that the lateral position and rotational orientation of the glutamic acid in the transmembrane domain does not correlate with transformation. However, the primary structure in the vicinity of Glu664 plays a significant role in this activation. Our results suggest that the Glu664 activation involves highly specific interactions in the transmembrane domain of p185.

Related Genes
neu
MeSH Terms
3T3 Cells Amino Acid Sequence Animals Base Sequence Blotting, Western Cell Membrane/metabolism Electrophoresis, Polyacrylamide Gel ErbB Receptors/genetics,metabolism Glioma/chemically induced,metabolism Glutamates/genetics Glutamic Acid Mice Molecular Sequence Data Mutagenesis, Site-Directed Neuroblastoma/chemically induced,metabolism Precipitin Tests Protein-Tyrosine Kinases/genetics,metabolism Proto-Oncogene Proteins/genetics,metabolism Rats Receptor, ErbB-2 Signal Transduction Valine/genetics
Chemicals
Glutamates Proto-Oncogene Proteins Glutamic Acid ErbB Receptors Protein-Tyrosine Kinases Receptor, ErbB-2 Valine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cao H
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.
Bangalore L
Bormann B J
Stern D F
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-03-00
Pages
923-32
Language
English
Region
England
NLM ID
8208664
PMCID
PMC556533
Subset
IM
Grants
NCI NIH HHS · CA45708 · United States
External Links
PubMed source PMC Full Text View journal details
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