Fig. 8. Scheme to explain the role of Y359 and Y904 in regulating kAE1 localisation. kAE1 has two tyrosine residues, one in the N-terminus and one in the C-terminus, that are critical for basolateral localisation. We have shown that both of these tyrosines Y359 and Y904 can be phosphorylated. We propose that when Y359 and Y904 are phosphorylated at the plasma membrane, this marks the protein for internalisation by endocytosis. If Y359 is phosphorylated we hypothesise that this recruits a phosphatase (in this case SHP-2 via SH2 domain interaction), which then dephosphorylates Y904, blocking phosphorylation specific internalisation or revealing the basolateral targeting motif for recycling kAE1 back to the plasma membrane.