ArticleThe EMBO journal1995
Mutational analysis of the Src SH3 domain: the same residues of the ligand binding surface are important for intra- and intermolecular interactions.
Article in The EMBO journal, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 162 citations in OpenAlex.
- Phosphorylation of tyrosine 90 in SH3 domain is a new regulatory switch controlling Src kinase.eLife · 2023Article
- SHP-1 tyrosine phosphatase binding to c-Src kinase phosphor-dependent conformations: A comparative structural framework.PloS one · 2023Article
- A functional interaction between liprin-α1 and B56γ regulatory subunit of protein phosphatase 2A supports tumor cell motility.Communications biology · 2022Article
- A Model for the Signal Initiation Complex Between Arrestin-3 and the Src Family Kinase Fgr.Journal of molecular biology · 2022Article
- Modeling ErbB2-p130Cas interaction to design new potential anticancer agents.Scientific reports · 2019Article
- SH3BP4 Regulates Intestinal Stem Cells and Tumorigenesis by Modulating β-Catenin Nuclear Localization.Cell reports · 2019Article
- Identification of a membrane-less compartment regulating invadosome function and motility.Scientific reports · 2018Article
- Achieving a Graded Immune Response: BTK Adopts a Range of Active/Inactive Conformations Dictated by Multiple Interdomain Contacts.Structure (London, England : 1993) · 2017Article
- Inhibition of N1-Src kinase by a specific SH3 peptide ligand reveals a role for N1-Src in neurite elongation by L1-CAM.Scientific reports · 2017Article
- HLJ1 is an endogenous Src inhibitor suppressing cancer progression through dual mechanisms.Oncogene · 2016Article
- Imatinib binding to human c-Src is coupled to inter-domain allostery and suggests a novel kinase inhibition strategy.Scientific reports · 2016Article
- Mutation of Vav1 adaptor region reveals a new oncogenic activation.Oncotarget · 2015Article
- SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family.Biochemistry · 2014Article
- Src-dependent Tks5 phosphorylation regulates invadopodia-associated invasion in prostate cancer cells.The Prostate · 2014Article
- Identification of two tyrosine residues required for the intramolecular mechanism implicated in GIT1 activation.PloS one · 2014Article
- Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites.Molecular biology of the cell · 2013Article
- Structure-based redesign of the binding specificity of anti-apoptotic Bcl-x(L).Journal of molecular biology · 2013Article
- SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling.Molecular cell · 2012Article
- SRC points the way to biomarkers and chemotherapeutic targets.Genes & cancer · 2012Article
- Identification of N-methyl-D-aspartic acid (NMDA) receptor subtype-specific binding sites that mediate direct interactions with scaffold protein PSD-95.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein tyrosine kinase c-Src is negatively regulated by phosphorylation of Tyr527 in its C-terminal tail. The repressed state is achieved through intramolecular interactions involving the phosphorylated tail, the Src homology 2 (SH2) domain and the SH3 domain. Both the SH2 and SH3 domains have also been shown to mediate the intermolecular interaction of Src with several proteins. To test which amino acids of the Src SH3 domain are important for these interactions, and whether the intra- and intermolecular associations involve the same residues, we carried out a detailed mutational analysis of the presumptive interaction surface. All mutations of conserved hydrophobic residues had an effect on both inter- and intramolecular interactions of the Src SH3 domain, although not all amino acids were equally important. Chimeric molecules in which the Src SH3 domain was replaced with those of spectrin or Lck showed derepressed kinase activity, whereas a chimera containing the Fyn SH3 domain was fully regulated. Since spectrin and Lck SH3 domains share the conserved hydrophobic residues characteristic of SH3 domains, other amino acids must be important for specificity. Mutational analysis of non- or semi-conserved residues in the RT and n-Src loops showed that some of these were also involved in inter- and intramolecular interactions. Stable transfection of selected SH3 domain mutants into NIH-3T3 cells showed that despite elevated levels of phosphotyrosine, the cells were morphologically normal, indicating that the SH3 domain was required for efficient transformation of NIH-3T3 cells by Src.
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