Regulation of the tyrosine kinase substrate Eps8 expression by growth factors, v-Src and terminal differentiation

Rita Gallo, Claudia Provenzano, Roberta Carbone, Pier Paolo Di Fiore, Loriana Castellani, Germana Falcone, Stefano Alemà

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

SH3-containing proteins are involved in signal transduction by a number of growth factor receptors and in the organization of the cytoskeleton. The recently identified Eps8 protein, which contains an SH3 domain, is coupled functionally and physically to the EGFR and is tyrosine phosphorylated by this receptor and other receptors as well. Here, we examined the regulation of eps8 expression in response to mitogenic or differentiative signals. We show that Eps8 is expressed at low levels in resting fibroblasts, but its expression is strongly induced during activation by serum, phorbol esters and the v-src oncogene. Conversely, expression of Eps8, but not of other EGFR substrates such as Shc or Eps15, is virtually extinguished in non-proliferating, terminally differentiated murine myogenic cells. The putative role of Eps8 protein as a v-Src substrate was analysed in murine fibroblasts and in quail myogenic cells expressing a temperature-sensitive variant of the tyrosine kinase. Tyrosine phosphorylation of Eps8 was detected only at the permissive temperature. A non-myristylated, transformation-defective mutant of v-Src did not phosphorylate Eps8, whereas it phosphorylated Shc. Together, these findings indicate that Eps8 may be a critical substrate of v-Src. They further establish Eps8 as an example of a signal transducer whose expression senses the balance between growth and differentiation and might, therefore, be involved in the determination of the phenotype.

Original languageEnglish
Pages (from-to)1929-1936
Number of pages8
JournalOncogene
Volume15
Issue number16
Publication statusPublished - 1997

Fingerprint

Protein-Tyrosine Kinases
Intercellular Signaling Peptides and Proteins
Fibroblasts
src Genes
Proteins
Quail
Temperature
src Homology Domains
Growth Factor Receptors
Phorbol Esters
Cytoskeleton
Transducers
Tyrosine
Signal Transduction
Phosphorylation
Phenotype
Growth
Serum
tyrosine receptor

Keywords

  • Differentiation
  • Eps8
  • Shc
  • Signal transduction
  • Tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Gallo, R., Provenzano, C., Carbone, R., Di Fiore, P. P., Castellani, L., Falcone, G., & Alemà, S. (1997). Regulation of the tyrosine kinase substrate Eps8 expression by growth factors, v-Src and terminal differentiation. Oncogene, 15(16), 1929-1936.

Regulation of the tyrosine kinase substrate Eps8 expression by growth factors, v-Src and terminal differentiation. / Gallo, Rita; Provenzano, Claudia; Carbone, Roberta; Di Fiore, Pier Paolo; Castellani, Loriana; Falcone, Germana; Alemà, Stefano.

In: Oncogene, Vol. 15, No. 16, 1997, p. 1929-1936.

Research output: Contribution to journalArticle

Gallo, R, Provenzano, C, Carbone, R, Di Fiore, PP, Castellani, L, Falcone, G & Alemà, S 1997, 'Regulation of the tyrosine kinase substrate Eps8 expression by growth factors, v-Src and terminal differentiation', Oncogene, vol. 15, no. 16, pp. 1929-1936.
Gallo R, Provenzano C, Carbone R, Di Fiore PP, Castellani L, Falcone G et al. Regulation of the tyrosine kinase substrate Eps8 expression by growth factors, v-Src and terminal differentiation. Oncogene. 1997;15(16):1929-1936.
Gallo, Rita ; Provenzano, Claudia ; Carbone, Roberta ; Di Fiore, Pier Paolo ; Castellani, Loriana ; Falcone, Germana ; Alemà, Stefano. / Regulation of the tyrosine kinase substrate Eps8 expression by growth factors, v-Src and terminal differentiation. In: Oncogene. 1997 ; Vol. 15, No. 16. pp. 1929-1936.
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