Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src

Nature. 1991 May 2;351(6321):69-72. doi: 10.1038/351069a0.


The protein-tyrosine kinase activity of the proto-oncogene product p60c-src is negatively regulated by the phosphorylation of a tyrosine residue close to the C terminus, tyrosine 527. The phosphorylation might be catalysed by a so-far-unidentified tyrosine kinase, distinct from p60c-src. Recently we purified a protein-tyrosine kinase that specifically phosphorylates tyrosine 527 of p60c-src from neonatal rat brain. We have now confirmed the specificity of this enzyme by using a mutant p60c-src that has a phenylalanine instead of tyrosine 527, and cloned a complementary DNA that encodes the enzyme. The enzyme is similar to kinases of the src family in that it has two conserved regions, Src-homology regions 2 and 3, upstream of a tyrosine kinase domain. The amino-acid identity of each region is no more than 47%, however, and the enzyme lacks phosphorylation sites corresponding to tyrosines 416 and 527 of p60c-src and has no myristylation signal. These results suggest that this protein-tyrosine kinase, which might negatively regulate p60c-src, represents a new type of tyrosine kinase.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Base Sequence
  • Brain / enzymology
  • Cloning, Molecular / methods
  • DNA / genetics*
  • DNA / isolation & purification
  • Genes, src*
  • Molecular Sequence Data
  • Open Reading Frames
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Rats
  • Sequence Homology, Nucleic Acid


  • DNA
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins pp60(c-src)

Associated data

  • GENBANK/X57450
  • GENBANK/X57451
  • GENBANK/X57452
  • GENBANK/X57453
  • GENBANK/X57454
  • GENBANK/X57455
  • GENBANK/X57688
  • GENBANK/X57689
  • GENBANK/X58631
  • GENBANK/X59436