Direct demonstration of an intramolecular SH2-phosphotyrosine interaction in the Crk protein

Article Abstract:

A study conducted on the phosphorylation of the mouse Crk adaptor protein shows that this process involves an interaction between the Src-homology-2 (SH2) domain of Crk with proteins containing phosphotyrosine (pTyr) occurring within a signalling molecule. The Crk molecule contains one SH2 and two SH3 domains and the site at which tyrosine phosphorylation takes place is the 221th residue in between the SH3 domains. The SH2-pTyr interaction probably suppresses intermolecular interactions of the SH3 domain with other molecules.

author: Rosen, Michael K., Pawson, Tony, Kay, Lewis E., Yamazaki, Toshio, Gish, Gerald D., Kay, Cyril M.
Proteins

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New impressions of Src and Hck

Article Abstract:

Researchers have identified the crystal structures of human c-Src and its close relative haematopoietic cell kinase (Hck). Phosphorylation of an inhibitory carboxy-terminal tyrosine residue was used to inactivate the kinase. Moreover, it was found out that binding of specific ligands to the Hck non-catalytic domains can stimulate the kinase activity of Hck. These discoveries highlight the extraordinary versatility of protein modules such as SH2, SH3 and PH domains.

author: Pawson, Tony

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Getting down to specifics

Article Abstract:

A degenerate peptide library incorporating a central tyrosine residue serves as a substrate to analyze the substrate-specificity of several protein-tyrosine kinases (PTK). The binding sites for the protein SH2 domains are the hydrophobic residues at P3 position, which are selected by all PTKs. The Fps/Fes, Src and Abl PTKs exhibit selectivity for the peptides that can be bound to their SH2 domains, implying a role for SH2 in substrate-specificity.

author: Pawson, Tony

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subjects list: Research, Phosphorylation, Binding sites (Biochemistry), Active sites (Biochemistry), Protein tyrosine kinase, Protein-tyrosine kinase
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