ArticleCancer science2016
C-terminal Src kinase-mediated EPIYA phosphorylation of Pragmin creates a feed-forward C-terminal Src kinase activation loop that promotes cell motility.
Article in Cancer science, 2016. 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, 47 citations in OpenAlex.
- 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
- Conditional T and NK cell antagonism by a giant and highly conserved orthopoxvirus virulence factor.Research square · 2026Article
- SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- PEAK1 maintains tight junctions in intestinal epithelial cells and resists colitis by inhibiting autophagy-mediated ZO-1 degradation.Nature communications · 2025Article
- Current understanding of PEAK family members in regulation of cellular signaling pathways and cancer therapy.Molecular and cellular biochemistry · 2025Review
- PRAG1 Condensation Drives Cell Contraction Under Stress.Biomolecules · 2025Article
- Activation of CAMK2 by pseudokinase PEAK1 represents a targetable pathway in triple negative breast cancer.Nature communications · 2025Article
- A comparative analysis of paxillin and Hic-5 proximity interactomes.Cytoskeleton (Hoboken, N.J.) · 2025Article
- The suppression of cell motility through the reduction of FAK activity and expression of cell adhesion proteins by hAMSCs secretome in MDA-MB-231 breast cancer cells.Investigational new drugs · 2024Article
- Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown.Neurology international · 2023Article
- 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
- Article
- Piquing our interest: Insights into the role of PEAK3 in signaling and disease.Science signaling · 2022Article
- CK2β Is a Gatekeeper of Focal Adhesions Regulating Cell Spreading.Frontiers in molecular biosciences · 2022Article
- Article
- Host Genome-Wide Association Study of Infant Susceptibility toInfection and immunity · 2021Article
- Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis.Cancers · 2020Review
- Review
- 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
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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
Pragmin is one of the few mammalian proteins containing the Glu-Pro-Ile-Tyr-Ala (EPIYA) tyrosine-phosphorylation motif that was originally discovered in the Helicobacter pylori CagA oncoprotein. Following delivery into gastric epithelial cells by type IV secretion and subsequent tyrosine phosphorylation at the EPIYA motifs, CagA serves as an oncogenic scaffold/adaptor that promiscuously interacts with SH2 domain-containing mammalian proteins such as the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) and the C-terminal Src kinase (Csk), a negative regulator of Src family kinases. Like CagA, Pragmin also forms a physical complex with Csk. In the present study, we found that Pragmin directly binds to Csk by the tyrosine-phosphorylated EPIYA motif. The complex formation potentiates kinase activity of Csk, which in turn phosphorylates Pragmin on tyrosine-238 (Y238), Y343, and Y391. As Y391 of Pragmin comprises the EPIYA motif, Pragmin-Csk interaction creates a feed-forward regulatory loop of Csk activation. Together with the finding that Pragmin and Csk are colocalized to focal adhesions, these observations indicate that the Pragmin-Csk interaction, triggered by Pragmin EPIYA phosphorylation, robustly stimulates the kinase activity of Csk at focal adhesions, which direct cell-matrix adhesion that regulates cell morphology and cell motility. As a consequence, expression of Pragmin and/or Csk in epithelial cells induces an elongated cell shape with elevated cell scattering in a manner that is mutually dependent on Pragmin and Csk. Deregulation of the Pragmin-Csk axis may therefore induce aberrant cell migration that contributes to tumor invasion and metastasis.
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