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PMID: 1674818 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The juxtamembrane regions of the epidermal growth factor receptor and gp185erbB-2 determine the specificity of signal transduction.

Molecular and cellular biology ·Vol. 11 ·No. 6 ·1991-06-00 ·Pages 3191-202

Segatto O, Lonardo F, Wexler D, Fazioli F, Pierce JH, Bottaro DP, White MF, Di Fiore PP

Abstract

The epidermal growth factor receptor (EGFR) and gp185erbB-2 are closely related tyrosine kinases. Despite extensive sequence and structural homology, these two receptors display quantitative and qualitative differences in their ability to couple with mitogenic signalling pathways. By using chimeric molecules between EGFR and erbB-2, we found that the determinants responsible for the specificity of mitogenic signal transduction are located in the amino-terminal half of the tyrosine kinase domain of either receptor. In the EGFR, mutational analysis within this subdomain revealed that deletion of residues 660 to 667 impaired receptor mitogenic activity without affecting its tyrosine kinase properties. This sequence is therefore likely to contribute to the specificity of substrate recognition by the EGFR kinase.

MeSH Terms
Amino Acid Sequence Animals Cell Division Cell Line Cell Membrane/physiology ErbB Receptors/genetics,physiology Genetic Variation Genetic Vectors Mice Molecular Sequence Data Mutagenesis, Site-Directed Protein-Tyrosine Kinases/physiology Proto-Oncogene Proteins/genetics,physiology Receptor, ErbB-2 Signal Transduction Transfection
Chemicals
Proto-Oncogene Proteins ErbB Receptors Protein-Tyrosine Kinases Receptor, ErbB-2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Segatto O
Laboratory of Molecular and Cellular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Lonardo F
Wexler D
Fazioli F
Pierce J H
Bottaro D P
White M F
Di Fiore P P
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.11.6.3191-3202.1991
Published
1991-06-00
Pages
3191-202
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360172
Subset
IM
Grants
NIDDK NIH HHS · DK38712 · United States
External Links
PubMed source DOI: 10.1128/mcb.11.6.3191-3202.1991 PMC Full Text View journal details
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