Structural Basis for the Recognition of c-Src by Its Inactivator Csk

Nicholas M. Levinson, Markus A. Seeliger, Philip A. Cole, John Kuriyan

Research output: Contribution to journalArticle

Abstract

The catalytic activity of the Src family of tyrosine kinases is suppressed by phosphorylation on a tyrosine residue located near the C terminus (Tyr 527 in c-Src), which is catalyzed by C-terminal Src Kinase (Csk). Given the promiscuity of most tyrosine kinases, it is remarkable that the C-terminal tails of the Src family kinases are the only known targets of Csk. We have determined the crystal structure of a complex between the kinase domains of Csk and c-Src at 2.9 Å resolution, revealing that interactions between these kinases position the C-terminal tail of c-Src at the edge of the active site of Csk. Csk cannot phosphorylate substrates that lack this docking mechanism because the conventional substrate binding site used by most tyrosine kinases to recognize substrates is destabilized in Csk by a deletion in the activation loop.

Original languageEnglish (US)
Pages (from-to)124-134
Number of pages11
JournalCell
Volume134
Issue number1
DOIs
StatePublished - Jul 11 2008

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src-Family Kinases
Protein-Tyrosine Kinases
Phosphotransferases
Substrates
Phosphorylation
Tyrosine
CSK tyrosine-protein kinase
Catalyst activity
Catalytic Domain
Crystal structure
Chemical activation
Binding Sites

Keywords

  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Levinson, N. M., Seeliger, M. A., Cole, P. A., & Kuriyan, J. (2008). Structural Basis for the Recognition of c-Src by Its Inactivator Csk. Cell, 134(1), 124-134. https://doi.org/10.1016/j.cell.2008.05.051

Structural Basis for the Recognition of c-Src by Its Inactivator Csk. / Levinson, Nicholas M.; Seeliger, Markus A.; Cole, Philip A.; Kuriyan, John.

In: Cell, Vol. 134, No. 1, 11.07.2008, p. 124-134.

Research output: Contribution to journalArticle

Levinson, NM, Seeliger, MA, Cole, PA & Kuriyan, J 2008, 'Structural Basis for the Recognition of c-Src by Its Inactivator Csk', Cell, vol. 134, no. 1, pp. 124-134. https://doi.org/10.1016/j.cell.2008.05.051
Levinson NM, Seeliger MA, Cole PA, Kuriyan J. Structural Basis for the Recognition of c-Src by Its Inactivator Csk. Cell. 2008 Jul 11;134(1):124-134. https://doi.org/10.1016/j.cell.2008.05.051
Levinson, Nicholas M. ; Seeliger, Markus A. ; Cole, Philip A. ; Kuriyan, John. / Structural Basis for the Recognition of c-Src by Its Inactivator Csk. In: Cell. 2008 ; Vol. 134, No. 1. pp. 124-134.
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