Enhanced activation of an amino-terminally truncated isoform of the voltage-gated proton channel HVCN1 enriched in malignant B cells

What is it about?

We find that human B lymphocytes express two isoforms of the voltage-gated proton channel, HVCN1 - the full-length 273 amino acid Long form, and a Short form lacking the first 20 amino acids. Short form channels respond more strongly to phosphorylation ("enhanced gating"). Normal B cells have mainly Long form, but B cells from 76 Chronic Lymphocytic Leukemia patients had high levels of Short form. Short form interacted weakly with the B cell Receptor (BCR), hence was internalized less upon BCR activation. The properties of Short form suggest that a contribution to the pathology of CLL and other B cell malignancies.

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