Fig 1. Schematic representation of CD44 cleavage induced by phorbol ester (TPA).

The first cleavage step is mediated by membrane-associated matrix metalloproteases (predominantly by ADAM10) and leads to the release of the ectodomain into the extracellular space. The remaining CD44ΔE fragment is cleaved by γ-secretase which leads to the release of the intracellular domain (CD44-ICD) inside of the cell.