3lck

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{{STRUCTURE_3lck| PDB=3lck | SCENE= }}
{{STRUCTURE_3lck| PDB=3lck | SCENE= }}
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'''THE KINASE DOMAIN OF HUMAN LYMPHOCYTE KINASE (LCK), ACTIVATED FORM (AUTO-PHOSPHORYLATED ON TYR394)'''
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===THE KINASE DOMAIN OF HUMAN LYMPHOCYTE KINASE (LCK), ACTIVATED FORM (AUTO-PHOSPHORYLATED ON TYR394)===
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==Overview==
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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 basis for inhibition by phosphorylation at Tyr 505.
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(as it appears on PubMed at http://www.pubmed.gov), where 8945479 is the PubMed ID number.
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{{ABSTRACT_PUBMED_8945479}}
==Disease==
==Disease==
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[[Category: Signal transduction]]
[[Category: Signal transduction]]
[[Category: Tyrosine-protein kinase]]
[[Category: Tyrosine-protein kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 12:52:46 2008''

Revision as of 09:52, 3 July 2008

Image:3lck.png

Template:STRUCTURE 3lck

Contents

THE KINASE DOMAIN OF HUMAN LYMPHOCYTE KINASE (LCK), ACTIVATED FORM (AUTO-PHOSPHORYLATED ON TYR394)

Template:ABSTRACT PUBMED 8945479

Disease

Known disease associated with this structure: SCID due to LCK deficiency OMIM:[153390]

About this Structure

3LCK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation., Yamaguchi H, Hendrickson WA, Nature. 1996 Dec 5;384(6608):484-9. PMID:8945479

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