Phosphorylation and regulatory effects of the carboxy terminus of a Drosophila src homolog

Oncogene. 1992 Aug;7(8):1577-86.


The kinase activities of the vertebrate src family members are repressed by phosphorylation of a tyrosine residue in the carboxy-terminal 'tail' of these molecules. To explore whether the tail of an invertebrate src homolog might also serve a regulatory function, we examined the ability of the carboxy terminus of a Drosophila src homolog (p62D), which contains a tyrosine homologous to those in the vertebrate src family members, to regulate the following molecules in mammalian fibroblasts: (1) a chimeric protein, p60CD, containing the amino terminus and catalytic domains of chicken p60c-src joined to the C-terminus of p62D; and (2) full-length p62D itself. By a variety of criteria p60CD appears to be a partially, rather than fully, repressed form of p60c-src. Phosphopeptide mapping indicates that partial repression correlates with partial phosphorylation of the tyrosine in the p62D tail of the chimera. Phosphorylation of the tail may also regulate full-length p62D. Expression of p62D in fibroblasts does not affect cell morphology or the overall abundance of tyrosine-phosphorylated proteins. The molecule is phosphorylated at its C-terminal tyrosine (Tyr-547), but not at its in vitro autophosphorylation sites, suggesting that it is catalytically repressed in fibroblasts. Expression of a truncated p62D mutant lacking Tyr-547 is associated with a clear alteration in cellular morphology and a two- to threefold increase in cellular phosphotyrosine levels. These results suggest that phosphorylation of the C-terminal tyrosine of the tail of an invertebrate src-like kinase can repress the activity of adjacent catalytic domains.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Cell Line
  • Cloning, Molecular
  • Drosophila / chemistry*
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins*
  • Molecular Sequence Data
  • Oncogene Protein pp60(v-src) / chemistry
  • Oncogene Protein pp60(v-src) / genetics
  • Oncogene Protein pp60(v-src) / metabolism
  • Peptide Mapping
  • Phosphorylation
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Nucleic Acid


  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Protein-Tyrosine Kinases
  • Oncogene Protein pp60(v-src)
  • Src64B protein, Drosophila