Structure and regulation of Src family kinases
Abstract
Src family kinases are prototypical modular signaling proteins. Their conserved domain organization includes a myristoylated N-terminal segment followed by SH3, SH2, and tyrosine kinase domains, and a short C-terminal tail. Structural dissection of Src kinases has elucidated the canonical mechanisms of phosphotyrosine recognition by the SH2 domain and proline-motif recognition by the SH3 domain. Crystallographic analysis of nearly intact Src kinases in the autoinhibited state has shown that these protein interaction motifs turn inward and lock the kinase in an inactive conformation via intramolecular interactions. The autoinhibited Src kinase structures reveal a mode of domain assembly used by other tyrosine kinases outside the Src family, including Abl and likely Tec family kinases. Furthermore, they illustrate the underlying regulatory principles that have proven to be general among diverse modular signaling proteins. Although there is considerable structural information available for the autoinhibited conformation of Src kinases, how they may assemble into active signaling complexes with substrates and regulators remains largely unexplored.
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Src kinase is a non-receptor tyrosine kinase that is constitutively membrane-localised due to myristoylation at its N-terminus.
“Src kinase is a non-receptor tyrosine kinase that is constitutively membrane-localised due to myristoylation at its N-terminus [65].”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [65]
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- Authors
- Boggon, T. J., & Eck, M. J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Eck, Michael J
- Venue
- Oncogene
- Published
- 2004-10-18
- Volume
- 23
- Issue
- 48
- Pages
- 7918-7927
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1964396270
- Cited by
- 712
- References
- 0
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 41 · 2023: 23 · 2022: 41 · 2021: 29 · 2020: 46 · 2019: 31 · 2018: 31 · 2017: 45 · 2016: 37 · 2015: 27 · 2014: 33 · 2013: 34 · 2012: 33
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- Src family kinases, kinase autoinhibition, SH2 domain, SH3 domain, tyrosine kinase domain, myristoylation, phosphotyrosine recognition, intramolecular interactions, c-Abl, Tec kinase, kinase regulation
- MeSH terms
- Animals, Humans, Protein Structure, Tertiary, src-Family Kinases, Sequence Analysis, Protein
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