A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase

K. M V Lai, J. P. Olivier, G. D. Gish, M. Henkemeyer, J. McGlade, T. Pawson

Research output: Contribution to journalArticle

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Abstract

Antibodies to the human Shc adaptor protein were used to isolate a cDNA encoding a Drosophila Shc protein (dShc) by screening an expression library. The dshc gene, which maps to position 67B-C on the third chromosome, encodes a 45-kDa protein that is widely expressed throughout the Drosophila life cycle. In flies, the dShc protein physically associates with the activated Drosophila epidermal growth factor receptor homolog (DER) and is inducibly phosphorylated on tyrosine by DER. The 45-kDa dShc protein is closely related both in overall organization and in amino acid sequence (46% identity) to the 52-kDa mammalian Shc isoform. In addition to a C-terminal Src homology 2 (SH2) domain, dShc contains an N-terminal phosphotyrosine-binding (PTB) domain, which associates in vitro with the autophosphorylated DER receptor tyrosine kinase and with phosphopeptides containing an Asn-Pro-X-pTyr motif, where pTyr stands for phosphotyrosine. A potential binding site for the dShc PTB domain is located at Tyr-1228 of DER. These results indicate that the shc gene has been conserved in evolution, as have the binding properties of the Shc PTB and SH2 domains. Despite the close relationship between the Drosophila and mammalian Shc proteins, dShc lacks the high-affinity Grb2-binding site found in mammalian Shc, suggesting that Shc proteins may have functions in addition to regulation of the Ras pathway.

Original languageEnglish (US)
Pages (from-to)4810-4818
Number of pages9
JournalMolecular and Cellular Biology
Volume15
Issue number9
StatePublished - 1995

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Receptor Protein-Tyrosine Kinases
Drosophila
Phosphotyrosine
Genes
src Homology Domains
Shc Signaling Adaptor Proteins
Proteins
Binding Sites
Phosphopeptides
Drosophila Shc protein
Life Cycle Stages
Protein Binding
Diptera
Tyrosine
Amino Acid Sequence
Protein Isoforms
Complementary DNA
Chromosomes
Antibodies

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Lai, K. M. V., Olivier, J. P., Gish, G. D., Henkemeyer, M., McGlade, J., & Pawson, T. (1995). A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase. Molecular and Cellular Biology, 15(9), 4810-4818.

A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase. / Lai, K. M V; Olivier, J. P.; Gish, G. D.; Henkemeyer, M.; McGlade, J.; Pawson, T.

In: Molecular and Cellular Biology, Vol. 15, No. 9, 1995, p. 4810-4818.

Research output: Contribution to journalArticle

Lai, KMV, Olivier, JP, Gish, GD, Henkemeyer, M, McGlade, J & Pawson, T 1995, 'A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase', Molecular and Cellular Biology, vol. 15, no. 9, pp. 4810-4818.
Lai, K. M V ; Olivier, J. P. ; Gish, G. D. ; Henkemeyer, M. ; McGlade, J. ; Pawson, T. / A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase. In: Molecular and Cellular Biology. 1995 ; Vol. 15, No. 9. pp. 4810-4818.
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