Catalytic specificity of protein-tyrosine kinases is critical for selective signalling View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1995-02

AUTHORS

Zhou Songyang, Kermit L. Carraway, Michael J. Eck, Stephen C. Harrison, Ricardo A. Feldman, Moosa Mohammadi, Joseph Schlessinger, Stevan R. Hubbard, Darrin P. Smith, Charis Eng, Marla J. Lorenzo, Bruce A. J. Ponder, Bruce J. Mayer, Lewis C. Cantley

ABSTRACT

HOW do distinct protein-tyrosine kinases activate specific downstream events? Src-homology-2 (SH2) domains on tyrosine kinases or targets of tyrosine kinases recognize phosphotyrosine in a specific sequence context and thereby provide some specificity1–3. The role of the catalytic site of tyrosine kinases in determining target specificity has not been fully investigated. Here we use a degenerate peptide library to show that each of nine tyrosine kinases investigated has a unique optimal peptide substrate. We find that the cytosolic tyrosine kinases preferentially phosphorylate peptides recognized by their own SH2 domains or closely related SH2 domains (group I; ref. 3), whereas receptor tyrosine kinases preferentially phosphorylate peptides recognized by subsets of group III SH2 domains3. The importance of these findings for human disease is underscored by our observation that a point mutation in the RET receptor-type tyrosine kinase, which causes multiple endocrine neoplasia type 2B, results in a shift in peptide substrate specificity. More... »

PAGES

536-539

Journal

TITLE

Nature

ISSUE

6514

VOLUME

373

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/373536a0

    DOI

    http://dx.doi.org/10.1038/373536a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1041062008

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/7845468


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