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PMID: 7689153 Published · ppublish English Comparative Study Journal Article

eps15, a novel tyrosine kinase substrate, exhibits transforming activity.

Molecular and cellular biology ·Vol. 13 ·No. 9 ·1993-09-00 ·Pages 5814-28

Fazioli F, Minichiello L, Matoskova B, Wong WT, Di Fiore PP

Abstract

An expression cloning method which allows direct isolation of cDNAs encoding substrates for tyrosine kinases was applied to the study of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway. A previously undescribed cDNA was isolated and designated eps15. The structural features of the predicted eps15 gene product allow its subdivision into three domains. Domain I contains signatures of a regulatory domain, including a candidate tyrosine phosphorylation site and EF-hand-type calcium-binding domains. Domain II presents the characteristic heptad repeats of coiled-coil rod-like proteins, and domain III displays a repeated aspartic acid-proline-phenylalanine motif similar to a consensus sequence of several methylases. Antibodies specific for the eps15 gene product recognize two proteins: a major species of 142 kDa and a minor component of 155 kDa, both of which are phosphorylated on tyrosine following EGFR activation by EGF in vivo. EGFR is also able to directly phosphorylate the eps15 product in vitro. In addition, phosphorylation of the eps15 gene product in vivo is relatively receptor specific, since the erbB-2 kinase phosphorylates it very inefficiently. Finally, overexpression of eps15 is sufficient to transform NIH 3T3 cells, thus suggesting that the eps15 gene product is involved in the regulation of mitogenic signals.

Related Genes
eps15
MeSH Terms
3T3 Cells Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Base Sequence Calcium-Binding Proteins/genetics,metabolism Cell Compartmentation Cell Division Cell Transformation, Neoplastic Cloning, Molecular ErbB Receptors/metabolism Intracellular Signaling Peptides and Proteins Mice Molecular Sequence Data Phosphoproteins/genetics,physiology Phosphotyrosine Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins/metabolism Receptor, ErbB-2 Sequence Alignment Signal Transduction Tyrosine/analogs & derivatives,metabolism
Chemicals
Adaptor Proteins, Signal Transducing Calcium-Binding Proteins Eps15 protein, mouse Intracellular Signaling Peptides and Proteins Phosphoproteins Proto-Oncogene Proteins Phosphotyrosine Tyrosine ErbB Receptors Protein-Tyrosine Kinases Receptor, ErbB-2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Fazioli F
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Minichiello L
Matoskova B
Wong W T
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.13.9.5814-5828.1993
Published
1993-09-00
Pages
5814-28
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360326
Subset
IM
Databases
GENBANK
L21768
External Links
PubMed source DOI: 10.1128/mcb.13.9.5814-5828.1993 PMC Full Text View journal details
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