The putative structure of huCD146 protein and mechanisms that CD146 regulates the survival of melanoma. A. The putative structure of huCD146 protein. The CD146 sequence has three conserved motifs: a KKGK motif, a PKC site and a C terminus. The anti-CD146 mAbs that recognise the cognate epitopes in the extracellular domain are shown in the schematic diagram. B. CD146 is involved in both inside-out and outside-in signalling. Activation of the PI3K–AKT pathway can up-regulate the cell surface expression of CD146 (inside-out), and the cell surface expression of CD146 can in turn activate the PI3K–AKT pathway (outside-in).