Hypothetical assembly of CD44v3/HB-EGF/erbB1/HAS/Hyal (hyalurosome) complex and the mechanism of RAL and HAFi-induced keratinocyte proliferation.

<p>Schematic representation of the assembly of the putative complex: HAFi mediates CD44v3 and heparan-sulfate-bound pro-HB-EGF aggregation, resulting in the recruitment and activation of an MMP/ADAM. RAL increases the endogenous HA production by induction of HAS which will contribute to the aggregation of CD44v3 and pro-HB-EGF and to the activation of MMP/ADAM. Pro-HB-EGF is cleaved by the MMP/ADAM and the resulting active moiety binds and activates erbB1, generating proliferation signals. Endogenous HA synthesis is controlled by HA-degrading enzyme hyaluronidase (Hyal).