Stimulation of Src family protein-tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase Cgamma2 activation in lymphoma B cells exposed to low energy electromagnetic fields.

The Journal of biological chemistry · 1998 · Unclear · Low evidence

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UnclearLow evidencePaper 5393

Study snapshot

PublicationThe Journal of biological chemistry · 1998

Study typein_vitro

Reported directionUnclear

Evidence ratingLow

Abstract

Here, we present evidence that exposure of DT40 lymphoma B cells to low energy electromagnetic field (EMF) results in a tyrosine kinase-dependent activation of phospholipase Cgamma2 (PLC-gamma2) leading to increased inositol phospholipid turnover. B cells rendered PLC-gamma2-deficient by targeted disruption of the PLC-gamma2 gene as well as PLC-gamma2-deficient cells reconstituted with Src homology domain 2 (SH2) domain mutant PLC-gamma2 did not show any increase in inositol-1,4,5-trisphosphate levels after EMF exposure, providing direct evidence that PLC-gamma2 is responsible for EMF-induced stimulation of inositol phospholipid turnover, and its SH2 domains are essential for this function. B cells rendered SYK-deficient by targeted disruption of the syk gene did not show PLC-gamma2 activation in response to EMF exposure. The C-terminal SH2 domain of SYK kinase is essential for its ability to activate PLC-gamma2. SYK-deficient cells reconstituted with a C-terminal SH2 domain mutant syk gene failed to elicit increased inositol phospholipid turnover after EMF exposure, whereas SYK-deficient cells reconstituted with an N-terminal SH2 domain mutant syk gene showed a normal EMF response. LYN kinase is essential for the initiation of this biochemical signaling cascade. Lymphoma B cells rendered LYN-deficient through targeted disruption of the lyn gene did not elicit enhanced inositol phospholipid turnover after EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) mouse fyn gene into LYN-deficient B cells restored their EMF responsiveness. B cells reconstituted with a SH2 domain mutant fyn gene showed a normal EMF response, whereas no increase in inositol phospholipid turnover in response to EMF was noticed in LYN-deficient cells reconstituted with a SH3 domain mutant fyn gene. Taken together, these results indicate that EMF-induced PLC-gamma2 activation is mediated by LYN-regulated stimulation of SYK, which acts downstream of LYN kinase and upstream of PLC-gamma2.

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro

Effect directionunclear

PopulationDT40 lymphoma B cells

Sample sizeNot supplied

ExposureNot supplied

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Exposure of DT40 lymphoma B cells to low energy EMF was associated with tyrosine kinase-dependent activation of PLC-gamma2 and increased inositol phospholipid turnover/IP3. Genetic disruption experiments indicated PLC-gamma2 (and its SH2 domains), SYK (requiring its C-terminal SH2 domain), and LYN are required for the EMF-induced signaling response, with FYN able to restore responsiveness in LYN-deficient cells when wild-type (but not kinase-dead) FYN was introduced.

Outcomes measured

PLC-gamma2 activation
inositol phospholipid turnover
inositol-1,4,5-trisphosphate (IP3) levels
tyrosine kinase/Src family kinase signaling (LYN, SYK, FYN) involvement
SH2/SH3 domain dependence in signaling response

Limitations

No EMF exposure parameters (e.g., frequency, intensity, SAR, duration) are provided in the abstract.
In vitro cell model; findings may not generalize to in vivo or human health outcomes.
Sample size and replication details are not stated in the abstract.

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": null,
    "source": null,
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": "DT40 lymphoma B cells",
  "sample_size": null,
  "outcomes": [
    "PLC-gamma2 activation",
    "inositol phospholipid turnover",
    "inositol-1,4,5-trisphosphate (IP3) levels",
    "tyrosine kinase/Src family kinase signaling (LYN, SYK, FYN) involvement",
    "SH2/SH3 domain dependence in signaling response"
  ],
  "main_findings": "Exposure of DT40 lymphoma B cells to low energy EMF was associated with tyrosine kinase-dependent activation of PLC-gamma2 and increased inositol phospholipid turnover/IP3. Genetic disruption experiments indicated PLC-gamma2 (and its SH2 domains), SYK (requiring its C-terminal SH2 domain), and LYN are required for the EMF-induced signaling response, with FYN able to restore responsiveness in LYN-deficient cells when wild-type (but not kinase-dead) FYN was introduced.",
  "effect_direction": "unclear",
  "limitations": [
    "No EMF exposure parameters (e.g., frequency, intensity, SAR, duration) are provided in the abstract.",
    "In vitro cell model; findings may not generalize to in vivo or human health outcomes.",
    "Sample size and replication details are not stated in the abstract."
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "electromagnetic field",
    "EMF",
    "DT40",
    "lymphoma B cells",
    "PLC-gamma2",
    "inositol phospholipid turnover",
    "IP3",
    "Src family kinases",
    "LYN",
    "SYK",
    "FYN",
    "tyrosine phosphorylation",
    "SH2 domain",
    "SH3 domain"
  ],
  "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1074/jbc.273.7.4035
PubMed: 9461594

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