Cytoplasmic protein tyrosine phosphatases, regulation and function: the roles of PTP1B and TC-PTP

Bourdeau, Annie; Dubé, Nadia; Tremblay, Michel L.

doi:10.1016/j.ceb.2005.02.001

Cited by 204 publications

(164 citation statements)

References 63 publications

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“…In addition, loss of PTP1B in p53-null mice increases susceptibility to B cell lymphomas (51). However, despite such growth inhibitory functions, PTP1B-null mice do not show an increase in spontaneous tumors, nor do they show increased IGF-1 receptor signaling (50). In contrast, PTP1B is highly expressed in some tumors, such as breast, and plays a positive role in signaling by the HER2 oncoprotein-tyrosine kinase.…”

Section: Discussionmentioning

confidence: 90%

“…Furthermore, it is now also clear that some individual PTPs may function either negatively or positively depending on context, with PTP1B serving as an excellent case in point (12,23). PTP1B is well established as an antagonist of signaling by insulin (by dephosphorylation of insulin receptor ␤-subunit and IRS-1) and leptin (by dephosphorylation of JAK PTKs) and is an established therapeutic target for diabetes and obesity (12,23,50). In the context of cancer, PTP1B is known to play a suppressive role in inhibiting the action of several growth factor receptor PTKs (23).…”

Section: Discussionmentioning

confidence: 99%

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Protein-tyrosine Phosphatase 1B Antagonized Signaling by Insulin-like Growth Factor-1 Receptor and Kinase BRK/PTK6 in Ovarian Cancer Cells*

Fan

Lin

Lucito³

et al. 2013

Journal of Biological Chemistry

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Background: Multiple signaling pathways are disrupted in ovarian cancer, but the role of protein phosphatases is not appreciated. Results: PTP1B antagonizes signaling by IGF-1R and BRK/PTK6 in ovarian cancer cells. Conclusion: Decreased expression of PTP1B in ovarian cancer cells promotes migration, invasion, proliferation, and survival. Significance: PTP1B, which dephosphorylates the insulin receptor and is an important therapeutic target in diabetes, may antagonize IGF-1-induced signaling in specific contexts.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Protein-tyrosine Phosphatase 1B Antagonized Signaling by Insulin-like Growth Factor-1 Receptor and Kinase BRK/PTK6 in Ovarian Cancer Cells*

Fan

Lin

Lucito³

et al. 2013

Journal of Biological Chemistry

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“…Of interest, the specific activity of two PTPs involved in the JAK/STAT and MEK/ERK sig- naling pathways, SHP-1 and PTP1B, was significantly lower in RAW Nramp-1 cells, which may contribute to the higher phosphorylation of MEK1/2, ERK1/2, and STAT1 and therefore to the enhanced NO production. Together with SHP-1 and PTP1B, TCPTP is involved in the regulation of JAK/STAT signaling (64,65,68,69). Although protein expression of TCPTP was observed in both RAW and RAW Nramp-1 (Fig.…”

Section: Discussionmentioning

confidence: 99%

NRAMP-1 Expression Modulates Protein-tyrosine Phosphatase Activity in Macrophages

Gómez

Tremblay

et al. 2007

Journal of Biological Chemistry

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NRAMP-1 (natural resistance-associated macrophage protein-1) has been associated with innate resistance to unrelated intracellular pathogen infections, up-regulation of proinflammatory phagocyte functions, and susceptibility to autoimmune diseases. It is still unclear how the divalent cation transport function of NRAMP-1 accounts for the associated pleiotropic effects. In this study, we evaluated the impact of murine macrophage NRAMP-1 expression on the activity of protein-tyrosine phosphatases (PTPs) as an upstream event contributing to the NRAMP-1 regulation of signal transduction and control of effector macrophage functions. Functional expression of NRAMP-1 results in lower macrophage PTP activity and increased protein phosphorylation. Decreased PTP activity is not a result of changes in protein expression but rather a reversible regulatory mechanism involving the interaction with NRAMP-1 metal substrates. In the context of intracellular infections, NRAMP-1 expression prevents full macrophage PTP induction by Leishmania infection, correlating with higher nitric oxide production and lower parasite survival. We suggest that NRAMP-1 divalent cation transport leads to transient inhibition of PTPs via direct PTP-metal interaction and/or by reactive oxygen speciesdependent PTP oxidation, consequently promoting positive signal transduction, as a backbone for the induction of proinflammatory phagocyte functions.NRAMP-1 (natural resistance-associated macrophage protein-1), previously known as Bcg/Ity/Lsh, and recently renamed Slc11a1) has been associated with host resistance to unrelated intracellular pathogens (1, 2), including Leishmania (3, 4), Mycobacterium (5), and Salmonella (6). It has also been associated with the up-regulation of proinflammatory macrophage (M) 3 functions, such as major histocompatibility complex II expression (7,8), KC chemokine (9, 10), interleukin-1␤ (9), tumor necrosis factor-␣ (11, 12), nitric oxide (NO) production (13,14), and increased respiratory burst (15, 16). NRAMP-1 is a pH-dependent divalent cation transporter (17) localized to the late endosome/lysosomal compartment of Ms from the reticuloendothelial system (18) and present in gelatinase-positive tertiary granules of neutrophils (19). Upon phagocytosis, NRAMP-1 is rapidly recruited to the phagolysosomal membrane, where it mediates the transport of Mn 2ϩ , Fe 2ϩ , Co 2ϩ , and potentially other metals, including Zn 2ϩ (20 -23). The direction of metal flux is still controversial (17,24,25); however, transport studies, sequence and structural similarities with NRAMP-2, topology and thermodynamic considerations suggest that metal transport occurs from the vesicular lumen to the cytoplasm (17). NRAMP-1 expression has been shown to promote phagosome maturation (26 -28). In addition, efflux of essential metals from the phagosome may restrain the pathogen's development by interfering with essential microbial enzymes, such as superoxide dismutase and/or by promoting the up-regulation of host proinflammatory molecules. Although more than...

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“…It is ubiquitously expressed, with highest levels in hematopoietic tissues (for a review, see Bourdeau et al 1 ). TC-PTP Ϫ/Ϫ mice appear physically normal until 10 to 14 days of age, at which time they progressively develop tissue mononuclear cell infiltrates.…”

Section: Introductionmentioning

confidence: 99%

“…TC-PTP has been shown to control cytokine signaling events by its negative action on the Janus kinase (Jak) and signal transducer and activator of transcription (Stat) pathways (reviewed by Bourdeau et al 1 ). This cascade is crucial for hematopoietic development and cellular response to growth factors.…”

Section: Introductionmentioning

confidence: 99%

TC-PTP–deficient bone marrow stromal cells fail to support normal B lymphopoiesis due to abnormal secretion of interferon-γ

Bourdeau

Dubé

Heinonen

et al. 2007

Blood

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The T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of the Jak/Stat cytokine signaling pathway. Our study shows that the absence of TC-PTP leads to an early bone marrow B-cell deficiency characterized by hindered transition from the pre-B cell to immature B-cell stage. This phenotype is intrinsic to the B cells but most importantly due to bone marrow stroma abnormalities. We found that bone marrow stromal cells from TC-PTP ؊ IntroductionThe T-cell protein tyrosine phosphatase (TC-PTP) is an intracellular enzyme encoded by Ptpn2. It is ubiquitously expressed, with highest levels in hematopoietic tissues (for a review, see Bourdeau et al 1 ). TC-PTP Ϫ/Ϫ mice appear physically normal until 10 to 14 days of age, at which time they progressively develop tissue mononuclear cell infiltrates. 2 Elevated levels of IFN-␥ can be measured at 19 days of age, 3 and the animals die between 21 and 35 days of age. TC-PTP Ϫ/Ϫ mice display defective hematopoiesis and immune function, characterized by anemia and splenomegaly secondary to sequestration of erythrocytes and accumulation of myeloid cells. 2 TC-PTP was also shown to interact with TRAF2 downstream of the TNF proinflammatory cytokine. This interaction inactivated Src and suppressed MAPK signaling. 4 TC-PTP has been identified as a critical regulator of colony-stimulating factor 1 (CSF-1) signaling and mononuclear phagocyte development. On CSF-1 stimulation, a deficiency in TC-PTP leads to enhanced tyrosine phosphorylation of the Grb2/Gab2/Shp2 complex by the CSF-1 receptor and increased activation of Erk. 5 These results identified TC-PTP as a key modulator of inflammatory signals as well as macrophage and lymphocyte functions.TC-PTP has been shown to control cytokine signaling events by its negative action on the Janus kinase (Jak) and signal transducer and activator of transcription (Stat) pathways (reviewed by Bourdeau et al 1 ). This cascade is crucial for hematopoietic development and cellular response to growth factors. 6 Using an in vitro approach, TC-PTP substrate-trapping mutant D/A was shown to interact with Jak1 and Jak3. 7 Stat1, Stat3, and Stat5a/5b were also identified as substrates for TC-PTP. [8][9][10] It is clear that TC-PTP is a key director of several cytokine-signaling pathways, and thus may be involved in the development of multiple hematopoietic lineages.Here, we report that bone marrow stromal cells from TC-PTP Ϫ/Ϫ mice secrete abnormally high levels of IFN-␥, resulting in constitutive phosphorylation of Stat1 in pre-B cells and altered B-cell development in the bone marrow. Our findings are novel and reflect the therapeutic potential of TC-PTP as a modulator of bone marrow stroma microenvironment that could be exploited in leukemia and other immune disorders. Materials and methods MiceGeneration of TC-PTP mutant mice was described previously. 2 Experiments were performed with mice on a mixed Balb/c-129SJ background and with mice backcrossed for 8 generation on Balb/c. All procedures were approved by the McGill University Rese...

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Cytoplasmic protein tyrosine phosphatases, regulation and function: the roles of PTP1B and TC-PTP

Cited by 204 publications

References 63 publications

Protein-tyrosine Phosphatase 1B Antagonized Signaling by Insulin-like Growth Factor-1 Receptor and Kinase BRK/PTK6 in Ovarian Cancer Cells*

Protein-tyrosine Phosphatase 1B Antagonized Signaling by Insulin-like Growth Factor-1 Receptor and Kinase BRK/PTK6 in Ovarian Cancer Cells*

NRAMP-1 Expression Modulates Protein-tyrosine Phosphatase Activity in Macrophages

TC-PTP–deficient bone marrow stromal cells fail to support normal B lymphopoiesis due to abnormal secretion of interferon-γ

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