Leucine 255 of Src couples intramolecular interactions to inhibition of catalysis.
作者： Giulio Superti-Furga , Stefania Gonfloni , Friedrich Frischknecht , Michael Way
DOI: 10.1038/11537
关键词:
摘要: The activity of the c-Src tyrosine kinase is regulated through intramolecular interactions between catalytic and SH2/SH3 domains. However, exact mechanism by which this occurs remains obscure. In crystal structure c-Src, peptide that links SH2 domain (SH2-CD linker) sandwiched latter SH3 domain. A residue in linker, Leu 255, inserts its side chain into a deep hydrophobic pocket present on surface To investigate possible regulatory role prominent interaction, we mutated 255 to different residues. We found length 'bulkiness' had profound influence regulation. Src-L255V was highly active but showed reduced accessibility vitro as well an altered localization vivo when compared other deregulated forms Src. Our analyses lead us suggest 255-pocket interaction critical component inhibition Src family kinases.
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