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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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 signalling, lack demonstrable tyrosine phosphorylation sites, suggesting that other modalities of receptor-transducer interactions exist. A candidate for investigating this type of association is p97(eps8), a recently described substrate for RTKs. p97(eps8) 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.

Original languageEnglish
Pages (from-to)723-729
Number of pages7
JournalOncogene
Volume10
Issue number4
Publication statusPublished - 1995

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Phosphotyrosine
Epidermal Growth Factor Receptor
Receptor Protein-Tyrosine Kinases
src Homology Domains
Transducers
Tyrosine
Phosphorylation
Proteins

Keywords

  • Binding
  • EGFR
  • eps 8
  • Juxtamembrane

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Castagnino, P., Biesova, Z., Wong, W. T., Fazioli, F., Gill, G. N., & Di Fiore, P. P. (1995). Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent. Oncogene, 10(4), 723-729.

Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent. / Castagnino, P.; Biesova, Z.; Wong, W. T.; Fazioli, F.; Gill, G. N.; Di Fiore, P. P.

In: Oncogene, Vol. 10, No. 4, 1995, p. 723-729.

Research output: Contribution to journalArticle

Castagnino, P, Biesova, Z, Wong, WT, Fazioli, F, Gill, GN & Di Fiore, PP 1995, 'Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent', Oncogene, vol. 10, no. 4, pp. 723-729.
Castagnino, P. ; Biesova, Z. ; Wong, W. T. ; Fazioli, F. ; Gill, G. N. ; Di Fiore, P. P. / Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent. In: Oncogene. 1995 ; Vol. 10, No. 4. pp. 723-729.
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AU - Di Fiore, P. P.

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