ArticleThe Journal of biological chemistry2018
The crystal structure of pseudokinase PEAK1 (Sugen kinase 269) reveals an unusual catalytic cleft and a novel mode of kinase fold dimerization.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- A tandem recruitment site in the pseudokinase scaffold PEAK3 is subject to phosphorylation-dependent regulation and cancer-associated mutations.The Journal of biological chemistry · 2026Article
- Current understanding of PEAK family members in regulation of cellular signaling pathways and cancer therapy.Molecular and cellular biochemistry · 2025Review
- Activation of CAMK2 by pseudokinase PEAK1 represents a targetable pathway in triple negative breast cancer.Nature communications · 2025Article
- Mechanism of human PINK1 activation at the TOM complex in a reconstituted system.Science advances · 2024Article
- Recent insights into the therapeutic strategies targeting the pseudokinase PTK7 in cancer.Oncogene · 2024Review
- Structural mapping of PEAK pseudokinase interactions identifies 14-3-3 as a molecular switch for PEAK3 signaling.Nature communications · 2023Article
- Structural insights into regulation of the PEAK3 pseudokinase scaffold by 14-3-3.Nature communications · 2023Article
- Looking lively: emerging principles of pseudokinase signaling.Trends in biochemical sciences · 2022Review
- PEAK1 Y635 phosphorylation regulates cell migration through association with Tensin3 and integrins.The Journal of cell biology · 2022Article
- Article
- Piquing our interest: Insights into the role of PEAK3 in signaling and disease.Science signaling · 2022Article
- Activation mechanism of PINK1.Nature · 2022Article
- Recent advances in targeting protein kinases and pseudokinases in cancer biology.Frontiers in cell and developmental biology · 2022Review
- Mapping of a N-terminal α-helix domain required for human PINK1 stabilization, Serine228 autophosphorylation and activation in cells.Open biology · 2022Article
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- Sequence assignment for low-resolution modelling of protein crystal structures.Acta crystallographica. Section D, Structural biology · 2019Article
- PEAK3/C19orf35 pseudokinase, a new NFK3 kinase family member, inhibits CrkII through dimerization.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Prospects for pharmacological targeting of pseudokinases.Nature reviews. Drug discovery · 2019Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The pseudokinase group encompasses some 10% of protein kinases, but pseudokinases diverge from canonical kinases in key motifs. The two members of the small new kinase family 3 (NKF3) group are considered pseudokinases. These proteins, pseudopodium-enriched atypical kinase 1 (PEAK1, Sugen kinase 269, or SgK269) and pragmin (Sugen kinase 223 or SgK223), act as scaffolds in growth factor signaling pathways, and both contain a kinase fold with degraded kinase motifs at their C termini. These kinases may harbor regions that mediate oligomerization or control other aspects of signal transduction, but a lack of structural information has precluded detailed investigations into their functional roles. In this study, we determined the X-ray crystal structure of the PEAK1 pseudokinase domain to 2.3 Å resolution. The structure revealed that the PEAK1 kinase-like domain contains a closed nucleotide-binding cleft that in this conformation may deleteriously affect nucleotide binding. Moreover, we found that N- and C-terminal extensions create a highly unusual all α-helical split-dimerization region, termed here the split helical dimerization (SHED) region. Sequence conservation analysis suggested that this region facilitates a dimerization mode that is conserved between PEAK1 and pragmin. Finally, we observed structural similarities between the PEAK1 SHED region and the C-terminal extension of the Parkinson's disease-associated kinase PINK1. In summary, PEAK1's kinase cleft is occluded, and its newly identified SHED region may promote an unexpected dimerization mode. Similarities of PEAK1 with the active kinase PINK1 may reclassify the latter as a member of the new kinase family 3 group.
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