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PDBsum entry 4tzi
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References listed in PDB file
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Key reference
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Title
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Tyrosine phosphorylation of the lyn src homology 2 (sh2) domain modulates its binding affinity and specificity.
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Authors
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L.L.Jin,
L.E.Wybenga-Groot,
J.Tong,
P.Taylor,
M.D.Minden,
S.Trudel,
C.J.Mcglade,
M.F.Moran.
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Ref.
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Mol Cell Proteomics, 2015,
14,
695-706.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Src homology 2 (SH2) domains are modular protein structures that bind
phosphotyrosine (pY)-containing polypeptides and regulate cellular functions
through protein-protein interactions. Proteomics analysis showed that the SH2
domains of Src family kinases are themselves tyrosine phosphorylated in blood
system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia,
and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we
found that phosphorylation at the conserved SH2 domain residue Y(194) impacts
the affinity and specificity of SH2 domain binding to pY-containing peptides and
proteins. Analysis of the Lyn SH2 domain crystal structure supports a model
wherein phosphorylation of Y(194) on the EF loop modulates the binding pocket
that engages amino acid side chains at the pY+2/+3 position. These data indicate
another level of regulation wherein SH2-mediated protein-protein interactions
are modulated by SH2 kinases and phosphatases.
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