ArticleProceedings of the National Academy of Sciences of the United States of America2005
Intramolecular interaction between phosphorylated tyrosine-783 and the C-terminal Src homology 2 domain activates phospholipase C-gamma1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 110 citations in OpenAlex.
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cold-Induced Urticarias with Familial Background: Clinical Spectrum, Pathogenesis, and Diagnostic Challenges.Diagnostics (Basel, Switzerland) · 2025Review
- Mammalian PI-Phospholipase C Isozymes: Structural and Functional Insights and Roles in Health and Disease.Medicina (Kaunas, Lithuania) · 2025Review
- A non-catalytic role of IPMK is required for PLCγ1 activation in T cell receptor signaling by stabilizing the PLCγ1-Sam68 complex.Cell communication and signaling : CCS · 2024Article
- Dynamics of allosteric regulation of the phospholipase C-γ isozymes upon recruitment to membranes.eLife · 2022Article
- A kinetic model of phospholipase C-γ1 linking structure-based insights to dynamics of enzyme autoinhibition and activation.The Journal of biological chemistry · 2022Article
- Receptor tyrosine kinases regulate signal transduction through a liquid-liquid phase separated state.Molecular cell · 2022Article
- Colchicine protects against cartilage degeneration by inhibiting MMP13 expression via PLC-γ1 phosphorylation.Osteoarthritis and cartilage · 2021Article
- Emerging roles of PLCγ1 in endothelial biology.Science signaling · 2021Review
- PLCγ1 promotes phase separation of T cell signaling components.The Journal of cell biology · 2021Article
- PD-L1 recruits phospholipase C and enhances tumorigenicity of lung tumors harboring mutant forms of EGFR.Cell reports · 2021Article
- Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Proteogenomic and metabolomic characterization of human glioblastoma.Cancer cell · 2021Article
- Autophosphorylation of EGFR at Y954 Facilitated Homodimerization and Enhanced Downstream Signals.Biophysical journal · 2020Article
- Fibroblast growth factor signalling in osteoarthritis and cartilage repair.Nature reviews. Rheumatology · 2020Review
- Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations.eLife · 2019Article
- PLC-gamma-1 phosphorylation status is prognostic of metastatic risk in patients with early-stage Luminal-A and -B breast cancer subtypes.BMC cancer · 2019Article
- T Cell Receptor (TCR)-Induced PLC-γ1 Sumoylation via PIASxβ and PIAS3 SUMO E3 Ligases Regulates the Microcluster Assembly and Physiological Function of PLC-γ1.Frontiers in immunology · 2019Article
- IL-17A-Mediated Excessive Autophagy Aggravated Neuronal Ischemic Injuries via Src-PP2B-mTOR Pathway.Frontiers in immunology · 2019Article
- Bridging the Gap: Modulatory Roles of the Grb2-Family Adaptor, Gads, in Cellular and Allergic Immune Responses.Frontiers in immunology · 2019Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phospholipase C-gamma1 (PLC-gamma1) contains two tandem Src homology 2 (SH2) domains. The NH(2)-terminal SH2 domain has been known to mediate the binding of PLC-gamma1 to receptor protein tyrosine kinases, which then activate PLC-gamma1 via phosphorylation at Y783. We now show that the phosphorylated Y783 residue (pY783) associates with the COOH-terminal SH2 domain [SH2(C)] within the same molecule of PLC-gamma1. The specificity of this intramolecular interaction is demonstrated in several ways. The mutation of SH2(C), but not of the NH(2)-terminal SH2 domain, exposes pY783 and makes it available for binding by anti-pY783 antibodies, for intermolecular association with a GST fusion protein containing the tandem SH2 domains of PLC-gamma1 and for dephosphorylation by phosphatases. The intramolecular interaction between pY783 and SH2(C) induces a rearrangement of surface charge such that PLC-gamma1 molecules phosphorylated at Y783 are retained more strongly by heparin resins than are unphosphorylated molecules. Finally, the intramolecular interaction of pY783 with SH2(C) results in activation of phospholipase activity. Our results thus clarify the molecular mechanism of PLC-gamma1 activation, revealing the specific function of pY783 and the distinct roles of the two SH2 domains in this process.
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