ALK is dephosphorylated by PTPRZ leading to loss of activity (Perez-Pinera et al, 2007). Some studies suggest that, rather than being canonically activated by direct binding of PTN and MDK, ALK is activated in a ligand-independent manner by the binding of these ligands to PTPRZ (and possibly PTPRB) instead. PTN- and MDK-binding to PTPRZ/B promotes their oligomerization and catalytic inactivation, thus inhibiting the phosphatase activity and allowing the autoactivation of ALK to predominate (Perez-Pinera et al, 2007; Fukada et al, 2006; Maeda et al, 1999; Kuboyama et al, 2016; reviewed in Deuel, 2013). Discrepancies between these two models remain to be worked out.
Chow, JP, Fukada, M, Ikematsu, S, Sakuma, S, Fujikawa, A, Noda, M
Maeda, N, Noda, M, Ichihara-Tanaka, K, Kadomatsu, K, Muramatsu, T, Kimura, T
Tanga, N, Kuboyama, K, Suzuki, R, Fujikawa, A, Noda, M
Deuel, TF
Deuel, TF, Chang, Y, Vega, JA, Zhang, W, Perez-Pinera, P
protein tyrosine phosphatase activity of C4S-PTPRZ1 [plasma membrane]
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