FLT3 p.Gln640SerfsTer8 signaling (Homo sapiens)

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1Cell Cycle ProgressionCCR5STAT3Chemotaxis to Mucosal &/or Inflammed Tissues3FLT3STAT3STAT3STAT3CCR6CCR5CCR63


Description

Germline variant FLT3 p.Gln640SerfsTer8 lacks the catalytic kinase domain. However, the frameshift variant encodes a truncated protein variant that contains a short cytoplasmic segment which harbours two SH2-binding STAT3 docking sites. This results in enhanced STAT3 tyrosine phosphorylation followed by increase STAT3-dependent transcription activity. Expression of FLT3 p.Gln640SerfsTer8 in T lymphoblast model cell line BW5147 results in increased proliferation and increased cell surface expression of inflammatory chemokine receptors CCR5 and CCR6, which are involved in migration of immune cells to mucosal tissues and inflamed areas.

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Bibliography

  1. Ulaganathan VK; ''TraPS-VarI: Identifying genetic variants altering phosphotyrosine based signalling motifs.''; Sci Rep, 2020 PubMed Europe PMC Scholia
  2. Yu H, Kortylewski M, Pardoll D; ''Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment.''; Nat Rev Immunol, 2007 PubMed Europe PMC Scholia
  3. ''Functional expression of chemokine receptor CCR6 on human effector memory CD8+ T cells ''; Eur J Immunol, 2007 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
129717view01:32, 22 May 2024EweitzModified title
129005view17:40, 2 March 2024KhanspersOntology Term : 'altered signaling pathway' added !
129004view17:38, 2 March 2024KhanspersOntology Term : 'signaling pathway pertinent to immunity' added !
127843view14:36, 23 December 2023EweitzModified title
127788view09:10, 12 December 2023Mkutmonadd ref info
127787view09:06, 12 December 2023MkutmonOntology Term : 'signaling pathway' added !
127773view18:34, 4 December 2023UlaganathanModified description
127766view10:07, 3 December 2023EgonwUse the main Uniprot datasource, to ensure link outs are working
127765view10:04, 3 December 2023EgonwMade a pathway clickable
127756view20:25, 2 December 2023UlaganathanNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
CCR5ProteinP51681 (Uniprot-TrEMBL)
CCR6ProteinP51684 (Uniprot-TrEMBL)
Cell Cycle ProgressionPathwayWP179 (WikiPathways)
Chemotaxis to Mucosal &/or Inflammed TissuesPathway
FLT3ProteinP36888 (Uniprot-TrEMBL)
STAT3ProteinP40763 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

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