Protein tyrosine phosphatases and the immune response

Mustelin, Tomas; Vang, Torkel; Bottini, Nunzio

doi:10.1038/nri1530

Cited by 313 publications

(286 citation statements)

References 135 publications

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“…Clearly, the full range of functions of PTPN22 remain to be defined, in terms of both signaling pathways and the cell types in which they act. Indeed, there is now an explosion of interest in phosphatases as regulators of a wide variety of cellular functions (21). More than 100 different tyrosine phosphatases have been defined; this exceeds the number of tyrosine kinases (14).…”

Section: Peter K Gregersen and Franak Batliwallamentioning

confidence: 99%

“…More than 100 different tyrosine phosphatases have been defined; this exceeds the number of tyrosine kinases (14). Although all of these molecules are likely to have interesting biologic effects (21), PTPN22 is now going to receive a high level of scrutiny, given its clear involvement in RA and other forms of autoimmunity.…”

Section: Peter K Gregersen and Franak Batliwallamentioning

confidence: 99%

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PTPN22 and rheumatoid arthritis: Gratifying replication

Gregersen¹,

Batliwalla²

2005

Arthritis & Rheumatism

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Section: Peter K Gregersen and Franak Batliwallamentioning

confidence: 99%

Section: Peter K Gregersen and Franak Batliwallamentioning

confidence: 99%

PTPN22 and rheumatoid arthritis: Gratifying replication

Gregersen¹,

Batliwalla²

2005

Arthritis & Rheumatism

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“…However, the phosphorylation modification of key proteins in PRRs signaling has not been fully elucidated. Protein tyrosine phosphatases (PTPs), which dephosphorylate tyrosine residues of target substrates (15,16), have been reported to be involved in the regulation of innate immune responses, such as Src homology region 2 domain-containing phosphatase-1 (17), Src homology region 2 domain-containing phosphatase-2 (18), PTPN22 (19), PTP with proline-glutamine-serine-threonine-rich motifs (20), PTP1B (21), and so on. However, the PTPs identified to be PRRs regulators possessed broadly regulatory effects and that limited their potential implication for immunotherapy.…”

mentioning

confidence: 99%

Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM

Huai

Song

Wang

et al. 2015

The Journal of Immunology

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TLR4 recruits TRIF-related adaptor molecule (TRAM, also known as TICAM2) as a sorting adaptor to facilitate the interaction between TLR4 and TRIF and then initiate TRIF-dependent IRF3 activation. However, the mechanisms by which TRAM links downstream molecules are not fully elucidated. In this study, we show that TRAM undergoes tyrosine phosphorylation upon TLR4 activation and that is required for TLR4-induced IRF3 activation. Protein tyrosine phosphatase nonreceptor type 4 (PTPN4), a protein tyrosine phosphatase, inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRAM, resulting in the disturbance of TRAM–TRIF interaction. Consequently, PTPN4 specifically inhibits TRIF-dependent IRF3 activation and IFN-β production in TLR4 pathway. Therefore, our results provide new insight into the TLR4 pathway and identify PTPN4 as a specific inhibitor of TRIF-dependent TLR4 pathway. Targeting PTPN4 would be beneficial for the development of new strategy to control TLR4-associated diseases without unwanted side effects.

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“…In fact, if the balance between PTPs and PTKs is disrupted and tyrosinephosphorylated proteins accumulate, abnormal proliferation and cell function may result [5].…”

Section: Introductionmentioning

confidence: 99%

Low expression of SHP-2 is associated with less favorable prostate cancer outcomes

et al. 2012

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Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is an important regulator of cell signaling because of its ability to dephosphorylate receptors of growth factors as well as the cytokines and tyrosine-phosphorylated proteins associated with these receptors. In the current study, we used four different prostate cancer cell lines: PC3, DU145, LNCaP and LNCaP-IL6+. Tumor specimens from 122 patients with prostate cancer were analyzed using a tissue microarray. Our data demonstrate that all four prostate cancer cell lines express the SHP-2 protein. Additionally, low staining intensity and SHP-2 expression in the cytoplasm of cancer cells in prostate tumor specimens was inversely correlated with prostate volume (p=0.041 and p=0.042, respectively) whereas nuclear staining was positively correlated with extracapsular extension (ece) (p=0.039). In our post-prostatectomy specimens, we found that patients with low SHP-2 expression had less-favorable outcomes with respect to biochemical recurrence (BCR) and clinical progression (p=0.005 and p=0.018 respectively). The loss of cytoplasmic SHP-2 expression is associated with increased growth and prostatic cancer progression.

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Protein tyrosine phosphatases and the immune response

Cited by 313 publications

References 135 publications

PTPN22 and rheumatoid arthritis: Gratifying replication

PTPN22 and rheumatoid arthritis: Gratifying replication

Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM

Low expression of SHP-2 is associated with less favorable prostate cancer outcomes

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