Protein tyrosine phosphatase receptor type Z is inactivated by ligand‐induced oligomerization

Fukada, Masahide; Fujikawa, Akihiro; Chow, Jeremy P.H.; Ikematsu, Shinya; Sakuma, Sadatoshi; Noda, Masaharu

doi:10.1016/j.febslet.2006.06.041

Cited by 80 publications

(82 citation statements)

References 31 publications

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“…MAGI proteins have previously been shown to interact with RPTPb. 28,29,39 We and others, 29,39 have observed that RPTPb can dephosphorylate MAGI proteins. In addition, we found that RPTPb, ERBB4 and MAGI proteins can colocalize in cells.…”

Section: Discussionmentioning

confidence: 95%

“…28,29 Furthermore, RPTPb has been shown to dephosphorylate tyrosinephosphorylated MAGI-1. 29,39 As our data indicated that MAGI proteins could bind and be phosphorylated by a tyrosine kinase (ERBB4), we sought to determine whether MAGI proteins could represent a functional (and possibly physical) link between a phosphotyrosine kinase and a phosphatase activity. We therefore transfected cells with ERBB2, ERBB4 and MAGI-1, in the presence or absence of RPTPb, and assayed the tyrosine phosphorylation of MAGI-1.…”

Section: Identification Of Magis As Erbb4-interacting Proteinsmentioning

confidence: 99%

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Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

et al. 2007

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Neuregulin and the neuregulin receptor ERBB4 have been genetically and functionally implicated in schizophrenia. In this study, we used the yeast two-hybrid system to identify proteins that interact with ERBB4, to identify genes and pathways that might contribute to schizophrenia susceptibility. We identified the MAGI scaffolding proteins as ERBB4-binding proteins. After validating the interaction of MAGI proteins with ERBB4 in mammalian cells, we demonstrated that ERBB4 expression, alone or in combination with ERBB2 or ERBB3, led to the tyrosine phosphorylation of MAGI proteins, and that this could be further enhanced with receptor activation by neuregulin. As MAGI proteins were previously shown to interact with receptor phosphotyrosine phosphatase b/f (RPTPb), we postulated that simultaneous binding of MAGI proteins to RPTPb and ERBB4 forms a phosphotyrosine kinase/phosphotyrosine phosphatase complex. Studies in cultured cells confirmed both a spatial and functional association between ERBB4, MAGI and RPTPb. Given the evidence for this functional association, we examined the genes coding for MAGI and RPTPb for genetic association with schizophrenia in a Caucasian United Kingdom case-control cohort (n = B1400). PTPRZ1, which codes for RPTPb, showed significant, gene-wide and hypothesis-wide association with schizophrenia in our study (best individual single-nucleotide polymorphism allelic P = 0.0003; gene-wide P = 0.0064; hypothesiswide P = 0.026). The data provide evidence for a role of PTPRZ1, and for RPTPb signaling abnormalities, in the etiology of schizophrenia. Furthermore, the data indicate a role for RPTPb in the modulation of ERBB4 signaling that may in turn provide further support for an important role of neuregulin/ERBB4 signaling in the molecular basis of schizophrenia.

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Section: Discussionmentioning

confidence: 95%

Section: Identification Of Magis As Erbb4-interacting Proteinsmentioning

confidence: 99%

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

et al. 2007

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“…Biochemical and structural lines of evidence suggest that dimerization of RPTPs is linked to inhibition of the phosphatase activity. In particular, PTPRZ is a catalytically active monomer on the cell surface in the absence of the growth factor pleiotrophin but becomes inactive after treatment with pleiotrophin induces dimerization of the ECD (27). Furthermore, the tandem phosphatase domains of PTPRG form stable dimers in solution, which occludes the catalytic site (28).…”

Section: Discussionmentioning

confidence: 99%

The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

Bouyain

Watkins

2010

Proc. Natl. Acad. Sci. U.S.A.

101

128

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The receptor protein tyrosine phosphatases gamma (PTPRG) and zeta (PTPRZ) are expressed primarily in the nervous system and mediate cell adhesion and signaling events during development. We report here the crystal structures of the carbonic anhydrase-like domains of PTPRZ and PTPRG and show that these domains interact directly with the second and third immunoglobulin repeats of the members of the contactin (CNTN) family of neural recognition molecules. Interestingly, these receptors exhibit distinct specificities: PTPRZ binds only to CNTN1, whereas PTPRG interacts with CNTN3, 4, 5, and 6. Furthermore, we present crystal structures of the four N-terminal immunoglobulin repeats of mouse CNTN4 both alone and in complex with the carbonic anhydrase-like domain of mouse PTPRG. In these structures, the N-terminal region of CNTN4 adopts a horseshoe-like conformation found also in CNTN2 and most likely in all CNTNs. This restrained conformation of the second and third immunoglobulin domains creates a binding site that is conserved among CNTN3, 4, 5, and 6. This site contacts a discrete region of PTPRG composed primarily of an extended β-hairpin loop found in both PTPRG and PTPRZ. Overall, these findings implicate PTPRG, PTPRZ and CNTNs as a group of receptors and ligands involved in the manifold recognition events that underlie the construction of neural networks.cell adhesion | crystal structure | Ig superfamily | receptor protein tyrosine phosphatase

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“…Pleiotrophin signals by inactivating its receptor, the Receptor Protein Tyrosine Phosphatase (RPTP)β/ζ [16,17]; the loss of the tyrosine phosphatase activity of RPTPβ/ζ in PTN-stimulated cells leaves tyrosine kinases that target the same sites normally dephosphorylated by RPTPβ/ ζ free to phosphorylate these same sites, thereby increasing levels of tyrosine phosphorylation of the different substrates of RPTPβ/ζ. The downstream targets of the PTN/RPTPβ/ζ signaling pathway and thus the substrates of RPTPβ/ζ include β-catenin [16], β-adducin [18,19], Fyn [20], GIT1/Cat-1 [21], and P190RhoGAP [22], proteins critical to functions of different cellular systems.…”

Section: Introductionmentioning

confidence: 99%

The receptor protein tyrosine phosphatase (RPTP)β/ζ is expressed in different subtypes of human breast cancer

Pérez-Piñera

García‐Suárez

Menéndez-Rodríguez

et al. 2007

Biochemical and Biophysical Research Communications

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Increasing evidence suggests mutations in human breast cancer cells that induce inappropriate expression of the 18kDa cytokine pleiotrophin (PTN, Ptn) initiate progression of breast cancers to a more malignant phenotype. Pleiotrophin signals through inactivating its receptor, the Receptor Protein Tyrosine Phosphatase (RPTP)β/ζ, leading to increased tyrosine phosphorylation of different substrate proteins of RPTPβ/ζ, including β-catenin, β-adducin, Fyn, GIT1/Cat-1, and P190RhoGAP. PTN signaling thus has wide impact on different important cellular systems. Recently, PTN was found to activate Anaplastic Lymphoma Kinase (ALK) through the PTN/RPTPβ/ζ signaling pathway; this discovery potentially is very important, since constitutive ALK activity of nucleophosmin (NPM)-ALK fusion protein is causative of anaplastic large cell lymphomas, and, activated ALK is found in other malignant cancers. Recently ALK was identified in each of 63 human breast cancers from 22 subjects. We now demonstrate that RPTPβ/ζ is expressed in each of these same 63 human breast cancers that previously were found to express ALK and in 10 additional samples of human breast cancer. RPTPβ/ζ furthermore was localized not only in its normal association with the cell membrane but also scattered in cytoplasm and in nuclei in different breast cancer cells and, in the case of infiltrating ductal carcinomas, the distribution of RPTPβ/ζ changes as the breast cancer become more malignant. The data suggest that the PTN/RPTPβ/ζ signaling pathway may be constitutively activated and potentially function to constitutively activate ALK in human breast cancer.

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Protein tyrosine phosphatase receptor type Z is inactivated by ligand‐induced oligomerization

Cited by 80 publications

References 31 publications

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

The receptor protein tyrosine phosphatase (RPTP)β/ζ is expressed in different subtypes of human breast cancer

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