Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation

Nature
H Yamaguchi, W A Hendrickson

Abstract

Regulation through phosphorylation is a characteristic of signalling pathways and the lymphocyte kinase Lck (p56lck) both performs phosphorylation and is affected by it. Lck is a Src-family tyrosine kinase expressed in T lymphocytes, where it participates in the cellular immune response. Like all Src homologues, it comprises SH3, SH2 and kinase domains. Lck associates through its distinctive amino-terminal segment with the cytoplasmic tails of either T-cell co-receptor, CD4 or CD8-alpha. Activated Lck phosphorylates T-cell receptor zeta-chains, which then recruit the ZAP70 kinase to promote T-cell activation. Lck is activated by autophosphorylation at Tyr 394 in the activation loop and it is inactive when Tyr 505 near the carboxy terminus is phosphorylated and interacts with its own SH2 domain. Here we report the crystal structure of the Lck tyrosine kinase domain (LCKK) in its activated state at 1.7 A resolution. The structure reveals how a phosphoryl group at Tyr 394 generates a competent active site. Comparisons with other kinase structures indicate that tyrosine phophophorylation and ligand binding may in general elicit two distinct hinge-like movements between the kinase subdomains. From modelling studies, we suggest a bas...Continue Reading

References

Jan 25, 1991·Cell·L C CantleyS Soltoff
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Oct 1, 1988·Journal of Cellular Biochemistry·R M PerlmutterC B Wilson
Jun 18, 1993·Cell·J A Cooper, B Howell
Dec 1, 1994·Current Opinion in Structural Biology·E J Goldsmith, M H Cobb
Dec 1, 1994·Current Opinion in Structural Biology·S CoxS S Taylor
Nov 1, 1994·Trends in Biochemical Sciences·H Sun, N K Tonks
Jan 1, 1994·Annual Review of Physiology·S H Francis, J D Corbin
Oct 1, 1993·Protein Science : a Publication of the Protein Society·J ZhengL F Ten Eyck
Aug 1, 1996·Nature Structural Biology·A A RussoN P Pavletich
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4

❮ Previous
Next ❯

Citations

Jun 1, 1997·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G Superti-Furga, S Gonfloni
Feb 20, 2008·Pflügers Archiv : European journal of physiology·Zhichuan Li, Zijian Xie
Nov 27, 2010·Journal of Molecular Modeling·Heike Meiselbach, Heinrich Sticht
Oct 9, 2008·Cell Biochemistry and Biophysics·Kanakadurga KundrapuRoy J Duhé
Nov 1, 2003·Bioorganic & Medicinal Chemistry Letters·John WityakJoel C Barrish
Oct 29, 2003·Current Opinion in Chemical Biology·Philip A ColeDongxia Wang
Apr 12, 2003·Analytical Biochemistry·Noriyuki YamamotoTakahiro Yasuda
Mar 22, 2003·Experimental Cell Research·Robert N JorissenAntony W Burgess
Jun 4, 1999·Progress in Biophysics and Molecular Biology·S R Hubbard
Aug 23, 2002·Pharmacology & Therapeutics·Richard A Engh, Dirk Bossemeyer
Aug 24, 1999·Pharmacology & Therapeutics·J M SowadskiR Karlsson
Jan 5, 2002·Biochimica Et Biophysica Acta·E B YangP Mack
Aug 27, 1999·Immunology Today·J D Ashwell, U D'Oro
Aug 27, 1999·Immunology Today·M L Thomas, E J Brown
Jul 13, 2000·Cellular Signalling·J M ElleryP J Nicholls
Dec 31, 2002·Current Opinion in Structural Biology·Stevan R Hubbard
Nov 5, 1997·Current Opinion in Structural Biology·K Moffat, Z Ren
Jan 22, 1998·Current Opinion in Structural Biology·F Sicheri, J Kuriyan
Sep 30, 2000·Bioorganic & Medicinal Chemistry Letters·L D ArnoldS E Ratnofsky
Sep 30, 2000·Bioorganic & Medicinal Chemistry Letters·A F BurchatG B Tometzki
May 7, 2002·Bioorganic & Medicinal Chemistry Letters·Ping ChenJoel C Barrish
Jul 11, 2003·Bioorganic & Medicinal Chemistry Letters·Jagabandhu DasJohn Wityak
Aug 28, 2003·Bioorganic & Medicinal Chemistry Letters·Raji SundaramoorthiManfred Weigele
Aug 28, 2003·Bioorganic & Medicinal Chemistry Letters·Yihan WangTomi K Sawyer
Jun 1, 1997·Trends in Cell Biology·S D, T S J
Dec 28, 1999·Trends in Cell Biology·A Sali, J Kuriyan
Jun 5, 1998·Trends in Biochemical Sciences·J C WilliamsM Saraste
Dec 26, 2001·Cytokine & Growth Factor Reviews·Jonathan M Ellery, Peter J Nicholls
Mar 9, 2004·Drug Discovery Today·Cheng Luo, Pauliina Laaja
Mar 10, 2009·Journal of the American Chemical Society·Jean-Philippe Demers, Anthony Mittermaier
Mar 28, 2012·The Journal of Physical Chemistry. B·He HuangCarol Beth Post
Dec 4, 2012·Nature Immunology·Jérémie RossyKatharina Gaus
Jun 2, 2004·Nature Reviews. Cancer·Timothy J Yeatman
Sep 3, 2004·Nature Reviews. Cancer·Nick J DibbClifford D Mol
Mar 26, 2013·Nature Reviews. Immunology·Rebecca J Brownlie, Rose Zamoyska
Feb 20, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sichun YangBenoît Roux

❮ Previous
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