FLT3 p.Gln640SerfsTer8 signaling pathway (WP5431)

Homo sapiens

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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.

Authors

Ulaganathan , Egon Willighagen , Martina Summer-Kutmon , Eric Weitz , and Kristina Hanspers

Activity

last edited

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

signaling pathway altered signaling pathway signaling pathway pertinent to immunity

Participants
Query Drugst.One

Label Type Compact URI Comment
CCR5 Protein uniprot:P51681
STAT3 Protein uniprot:P40763
FLT3 Protein uniprot:P36888
STAT3 Protein uniprot:P40763
STAT3 Protein uniprot:P40763
STAT3 Protein uniprot:P40763
CCR6 Protein uniprot:P51684
CCR5 Protein uniprot:P51681
CCR6 Protein uniprot:P51684

References

  1. Functional expression of chemokine receptor CCR6 on human effector memory CD8+ T cells. Kondo T, Takata H, Takiguchi M. Eur J Immunol. 2007 Jan;37(1):54–65. PubMed Europe PMC Scholia
  2. TraPS-VarI: Identifying genetic variants altering phosphotyrosine based signalling motifs. Ulaganathan VK. Sci Rep. 2020 May 21;10(1):8453. PubMed Europe PMC Scholia