WP5431 - FLT3 p.Gln640SerfsTer8 signaling - Homo sapiens

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.