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

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Abstract

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 (refs 1–11). The phosphorylation might be catalysed by a so-far-unidentified tyrosine kinase, distinct from p60c-src (ref. 7). Recently we purified a protein-tyrosine kinase that specifically phosphorylates tyrosine 527 of p60c-src from neonatal rat brain8,12,13. 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.

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Author notes

  1. Alasdair MacAuley and Jonathan A. Cooper: Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA

Authors and Affiliations

  1. Division of Protein Metabolism, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565, Japan

    Shigeyuki Nada, Masato Okada, Alasdair MacAuley, Jonathan A. Cooper & Hachiro Nakagawa

Authors
  1. Shigeyuki Nada
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  2. Masato Okada
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  3. Alasdair MacAuley
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  4. Jonathan A. Cooper
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  5. Hachiro Nakagawa
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Nada, S., Okada, M., MacAuley, A. et al. Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src. Nature 351, 69–72 (1991). https://doi.org/10.1038/351069a0

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  • DOI: https://doi.org/10.1038/351069a0

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