Reactome | PTPRZ dephosphorylates ligand-bound ALK dimers

PTPRZ dephosphorylates ligand-bound ALK dimers

Stable Identifier

R-HSA-9700200

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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PTPRZ dephosphorylates ligand-bound ALK dimers

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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.

Literature References

PubMed ID	Title	Journal	Year
16814777	Protein tyrosine phosphatase receptor type Z is inactivated by ligand-induced oligomerization Chow, JP, Fukada, M, Ikematsu, S, Sakuma, S, Fujikawa, A, Noda, M	FEBS Lett.	2006
10212223	A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a heparin-binding growth factor midkine. Involvement of arginine 78 of midkine in the high affinity binding to PTPzeta Maeda, N, Noda, M, Ichihara-Tanaka, K, Kadomatsu, K, Muramatsu, T, Kimura, T	J. Biol. Chem.	1999
27445335	Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity: PLEIOTROPHIN-PTPRZ-A SIGNALING IS INVOLVED IN OLIGODENDROCYTE DIFFERENTIATION Tanga, N, Kuboyama, K, Suzuki, R, Fujikawa, A, Noda, M	J. Biol. Chem.	2016
23777859	Anaplastic lymphoma kinase: "Ligand Independent Activation" mediated by the PTN/RPTPβ/ζ signaling pathway Deuel, TF	Biochim. Biophys. Acta	2013
17681947	Anaplastic lymphoma kinase is activated through the pleiotrophin/receptor protein-tyrosine phosphatase beta/zeta signaling pathway: an alternative mechanism of receptor tyrosine kinase activation Deuel, TF, Chang, Y, Vega, JA, Zhang, W, Perez-Pinera, P	J. Biol. Chem.	2007