Several signal transducers bind through their SH2 domains to phosphotyrosine-containing motifs present in receptor tyrosine kinases (RTKs). However, the juxtamembrane regions of the epidermal growth factor receptor (EGFR) and of the related erbB-2 protein, while important in mitogenic signaling, lack demonstrable tyrosine phosphorylation sites, suggesting that other modalities of receptor-transducer interactions exist. A candidate for investigating this type of association is p97eps8, a recently described substrate for RTKs. p97eps8 is phosphorylated by several RTKs, associates with EGFR in vivo and, upon overexpression, enhances the transduction of EGFR-mediated mitogenic signals. Here we report that eps8 binds directly to the juxtamembrane region of EGFR through a domain that does not bear resemblance to SH2 domains and by a mechanism that does not require the presence of phosphotyrosine residues. Thus, the physical association between EGFR and eps8 represents a novel interaction between RTKs and their substrates.

Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent / P. Castagnino, Z. Biesova, W. T. Wong, F. Fazioli, G. N. Gill, P. P. Di Fiore. - In: ONCOGENE. - ISSN 0950-9232. - 10:4(1995 Feb 16), pp. 723-9-729.

Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent

P. P. Di Fiore
Ultimo
1995

Abstract

Several signal transducers bind through their SH2 domains to phosphotyrosine-containing motifs present in receptor tyrosine kinases (RTKs). However, the juxtamembrane regions of the epidermal growth factor receptor (EGFR) and of the related erbB-2 protein, while important in mitogenic signaling, lack demonstrable tyrosine phosphorylation sites, suggesting that other modalities of receptor-transducer interactions exist. A candidate for investigating this type of association is p97eps8, a recently described substrate for RTKs. p97eps8 is phosphorylated by several RTKs, associates with EGFR in vivo and, upon overexpression, enhances the transduction of EGFR-mediated mitogenic signals. Here we report that eps8 binds directly to the juxtamembrane region of EGFR through a domain that does not bear resemblance to SH2 domains and by a mechanism that does not require the presence of phosphotyrosine residues. Thus, the physical association between EGFR and eps8 represents a novel interaction between RTKs and their substrates.
3T3 Cells; Animals; Phosphotyrosine; Receptor, Epidermal Growth Factor; Recombinant Proteins; Tyrosine; Amino Acid Sequence; Mice; Protein Binding; Structure-Activity Relationship; Receptor Protein-Tyrosine Kinases; Adaptor Proteins, Signal Transducing; Molecular Sequence Data; Cytoskeletal Proteins; Proteins; Signal Transduction
Settore MED/04 - Patologia Generale
16-feb-1995
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/196004
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