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PMID: 8264635 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An epidermal growth factor receptor/ret chimera generates mitogenic and transforming signals: evidence for a ret-specific signaling pathway.

Molecular and cellular biology ·Vol. 14 ·No. 1 ·1994-01-00 ·Pages 663-75

Santoro M, Wong WT, Aroca P, Santos E, Matoskova B, Grieco M, Fusco A, di Fiore PP

Abstract

A chimeric expression vector which encoded for a molecule encompassing the extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) and the intracellular domain of the ret kinase (EGFR/ret chimera) was generated. Upon ectopic expression in mammalian cells, the EGFR/ret chimera was correctly synthesized and transported to the cell surface, where it was shown capable of binding EGF and transducing an EGF-dependent signal intracellularly. Thus, the EGFR/ret chimera allows us to study the biological effects and biochemical activities of the ret kinase under controlled conditions of activation. Comparative analysis of the growth-promoting activity of the EGFR/ret chimera expressed in fibroblastic or hematopoietic cells revealed a biological phenotype clearly distinguishable from that of the EGFR, indicating that the two kinases couple with mitogenic pathways which are different to some extent. Analysis of biochemical pathways implicated in the transduction of mitogenic signals also evidenced significant differences between the ret kinase and other receptor tyrosine kinases. Thus, the sum of our results indicates the existence of a ret-specific pathway of mitogenic signaling.

Related Genes
EGFR ret
MeSH Terms
3T3 Cells/cytology,metabolism Animals Base Sequence Cell Division/genetics,physiology Cell Line DNA/genetics Drosophila Proteins ErbB Receptors/genetics,metabolism GTPase-Activating Proteins Humans Inositol/metabolism Mice Molecular Sequence Data Phospholipids/metabolism Protein Serine-Threonine Kinases/metabolism Proteins/metabolism Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Signal Transduction/genetics,physiology Transformation, Genetic
Chemicals
Drosophila Proteins GTPase-Activating Proteins Phospholipids Proteins Proto-Oncogene Proteins Recombinant Fusion Proteins Inositol DNA ErbB Receptors Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Ret protein, Drosophila Ret protein, mouse Protein Serine-Threonine Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Santoro M
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Università degli Studi di Napoli, Italy.
Wong W T
Aroca P
Santos E
Matoskova B
Grieco M
Fusco A
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.14.1.663-675.1994
Published
1994-01-00
Pages
663-75
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358416
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.14.1.663-675.1994 PMC Full Text View journal details
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