PTP1B and TC-PTP: novel roles in immune-cell signalingThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.

2006 ◽  
Vol 84 (7) ◽  
pp. 667-675 ◽  
Author(s):  
Paul D. Simoncic ◽  
C. Jane McGlade ◽  
Michel L. Tremblay
Keyword(s):  
Immune Response ◽  
Cell Signaling ◽  
Protein Tyrosine Phosphatase ◽  
Immune Cell ◽  
Second Messengers ◽  
Tyrosine Phosphatase ◽  
Special Issue ◽  
Substrate Specificities ◽  
Myeloid Development ◽  
Selection Of

It has recently been demonstrated that the protein tyrosine phosphatase (PTP) PTP1B and the T-cell PTP (TC-PTP) target several substrates involved in immune cell signaling. Recent data have furthered the view of these 2 PTP members as key regulators of the immune response. This review will focus on the substrate specificities of PTP1B and TC-PTP and their roles in immune cell signaling, and will discuss some new data implicating PTP1B and TC-PTP in myeloid development.

scholarly journals Crystal Structure of Low-Molecular-Weight Protein Tyrosine Phosphatase from Mycobacterium tuberculosis at 1.9-Å Resolution

2005 ◽  
Vol 187 (6) ◽  
pp. 2175-2181 ◽  
Author(s):  
Chaithanya Madhurantakam ◽  
Eerappa Rajakumara ◽  
Pooja Anjali Mazumdar ◽  
Baisakhee Saha ◽  
Devrani Mitra ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Active Site ◽  
Tyrosine Phosphatase ◽  
Chloride Ion ◽  
Low Molecular Weight ◽  
Molecular Weight Protein ◽  
Substrate Specificities ◽  
Protein Tyrosine ◽  
Weight Protein ◽  
Low Molecular Weight Protein

ABSTRACT The low-molecular-weight protein tyrosine phosphatase (LMWPTPase) belongs to a distinctive class of phosphotyrosine phosphatases widely distributed among prokaryotes and eukaryotes. We report here the crystal structure of LMWPTPase of microbial origin, the first of its kind from Mycobacterium tuberculosis. The structure was determined to be two crystal forms at 1.9- and 2.5-Å resolutions. These structural forms are compared with those of the LMWPTPases of eukaryotes. Though the overall structure resembles that of the eukaryotic LMWPTPases, there are significant changes around the active site and the protein tyrosine phosphatase (PTP) loop. The variable loop forming the wall of the crevice leading to the active site is conformationally unchanged from that of mammalian LMWPTPase; however, differences are observed in the residues involved, suggesting that they have a role in influencing different substrate specificities. The single amino acid substitution (Leu12Thr [underlined below]) in the consensus sequence of the PTP loop, C T GNICRS, has a major role in the stabilization of the PTP loop, unlike what occurs in mammalian LMWPTPases. A chloride ion and a glycerol molecule were modeled in the active site where the chloride ion interacts in a manner similar to that of phosphate with the main chain nitrogens of the PTP loop. This structural study, in addition to identifying specific mycobacterial features, may also form the basis for exploring the mechanism of the substrate specificities of bacterial LMWPTPases.

Role of Protein Tyrosine Phosphatase in Regulation of Cell Signaling Cascades Affecting Tumor Cell Growth: A Future Perspective as Anti- Cancer Drug Target

2021 ◽  
Vol 22 ◽  
Author(s):  
Archanalakshmi Kambaru ◽  
Nidhee Chaudhary
Keyword(s):  
Cell Growth ◽  
Cell Signaling ◽  
Cancer Cell ◽  
Protein Tyrosine Phosphatase ◽  
Drug Target ◽  
Tyrosine Phosphatase ◽  
Signaling Cascades ◽  
Cancer Drug ◽  
Protein Tyrosine ◽  
Anti Cancer

: Protein Tyrosine Phosphatase (PTP) superfamily is a key enzyme involved in the regulation of growth-related cell signaling cascades, such as the RAS/MAPK pathway, that directly affect cancer cell growth and metastasis. Several studies have indicated that the drug resistance observed in several late-stage tumors might also be affected by the levels of PTP in the cell. Hence, these phosphatases have been in the limelight for the past few decades as potential drug-targets and several promising drug candidates have been developed, even though none of these drugs have reached the market yet. In this review, we explore the potential of PTP as a viable anti-cancer drug target by studying PTPs, their regulation of several key cancer cell signaling pathways and how their levels affect various types of cancer. Furthermore, we present the current scenario of PTP as a molecular target and the various challenges faced in the development of PTP-targeting anti-cancer drugs.

scholarly journals The SPOT technique as a tool for studying protein tyrosine phosphatase substrate specificities

2009 ◽  
Vol 11 (10) ◽  
pp. 2326-2334 ◽  
Author(s):  
Xavier Espanel ◽  
Martine Huguenin-Reggiani ◽  
Rob Hooft van Huijsduijnen
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Substrate Specificities ◽  
Protein Tyrosine ◽  
Phosphatase Substrate

AMP-activated protein kinase — the fat controller of the energy railroadThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.

2006 ◽  
Vol 84 (7) ◽  
pp. 655-665 ◽  
Author(s):  
Gregory R. Steinberg ◽  
S. Lance Macaulay ◽  
Mark A Febbraio ◽  
Bruce E. Kemp
Keyword(s):  
Protein Kinase ◽  
Energy Demand ◽  
Second Messengers ◽  
Metabolic Stress ◽  
Special Issue ◽  
Endocrine Control ◽  
Fatty Acid Triglyceride ◽  
Amp Activated Protein Kinase ◽  
Major Mediator ◽  
Selection Of

AMP-activated protein kinase plays an important role in the regulation of lipid metabolism in response to metabolic stress and energy demand. It is also under endocrine control. AMPK acts at multiple steps and has a central role controlling fatty acid, triglyceride, and cholesterol synthesis, as well as the oxidation of fatty acids through direct phosphorylation effects and the control of gene transcription. As such, it can be considered to be the fat controller of the energy railroad. It is thought that AMPK may be a major mediator of the health benefits of exercise in mitigating the development of obesity and age-onset diseases.

scholarly journals Macrophages Compensate for Loss of Protein Tyrosine Phosphatase N2 in Dendritic Cells to Protect from Elevated Colitis

2021 ◽  
Vol 22 (13) ◽  
pp. 6820
Author(s):  
Larissa Hering ◽  
Egle Katkeviciute ◽  
Marlene Schwarzfischer ◽  
Anna Niechcial ◽  
Julianne B. Riggs ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lamina Propria ◽  
Protein Tyrosine Phosphatase ◽  
Immune Cell ◽  
Tyrosine Phosphatase ◽  
Cell Transfer ◽  
Protein Tyrosine ◽  
Dss Colitis ◽  
T Cell Transfer

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Mice lacking PTPN2 in dendritic cells (DCs) develop skin and liver inflammation by the age of 22 weeks due to a generalized loss of tolerance leading to uncontrolled immune responses. The effect of DC-specific PTPN2 loss on intestinal health, however, is unknown. The aim of this study was to investigate the DC-specific role of PTPN2 in the intestine during colitis development. PTPN2fl/flxCD11cCre mice were subjected to acute and chronic DSS colitis as well as T cell transfer colitis. Lamina propria immune cell populations were analyzed using flow cytometry. DC-specific PTPN2 deletion promoted infiltration of B and T lymphocytes, macrophages, and DCs into the lamina propria of unchallenged mice and elevated Th1 abundance during acute DSS colitis, suggesting an important role for PTPN2 in DCs in maintaining intestinal immune cell homeostasis. Surprisingly, those immune cell alterations did not translate into increased colitis susceptibility in acute and chronic DSS-induced colitis or T cell transfer colitis models. However, macrophage depletion by clodronate caused enhanced colitis severity in mice with a DC-specific loss of PTPN2. Loss of PTPN2 in DCs affects the composition of lamina propria lymphocytes, resulting in increased infiltration of innate and adaptive immune cells. However, this did not result in an elevated colitis phenotype, likely because increased infiltration of macrophages in the intestine upon loss of PTPN2 loss in DCs can compensate for the inflammatory effect of PTPN2-deficient DCs.

scholarly journals The roseoloviruses downregulate the protein tyrosine phosphatase PTPRC (CD45)

2020 ◽  
Author(s):  
Melissa L. Whyte ◽  
Kelsey Smith ◽  
Amanda Buchberger ◽  
Linda Berg Luecke ◽  
Lidya Handayani Tjan ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Human Herpesvirus ◽  
Murine Cytomegalovirus ◽  
Protein Tyrosine ◽  
Infected Cells

AbstractLike all herpesviruses, the roseoloviruses (HHV6A, -6B, and -7) establish lifelong infection within their host, requiring these viruses to evade host anti-viral responses. One common host-evasion strategy is the downregulation of host-encoded, surface-expressed glycoproteins. Roseoloviruses have been shown to evade host the host immune response by downregulating NK-activating ligands, MHC class I, and the TCR/CD3 complex. To more globally identify glycoproteins that are differentially expressed on the surface of HHV6A-infected cells, we performed cell surface capture of N-linked glycoproteins present on the surface of T cells infected with HHV6A, and compared these to proteins present on the surface of uninfected T cells. We found that the protein tyrosine phosphatase CD45 is downregulated in T cells infected with HHV6A. We also demonstrated that CD45 is similarly downregulated in cells infected with HHV-7. CD45 is essential for signaling through the T cell receptor and as such, is necessary for developing a fully functional immune response. Interestingly, the closely related β-herpesviruses human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) have also separately evolved unique mechanisms to target CD45. While HCMV and MCMV target CD45 signaling and trafficking, HHV6A acts to downregulate CD45 transcripts.ImportanceHuman herpesviruses-6 and -7 infect essentially 100% of the world’s population before the age of 5 and then remain latent or persistent in their host throughout life. As such, these viruses are among the most pervasive and stealthy of all viruses. Host immune cells rely on the presence of surface-expressed proteins to identify and target virus-infected cells. Here, we investigated the changes that occur to proteins expressed on the cell surface of T cells after infection with human herpesvirus-6A. We discovered that HHV-6A infection results in a reduction of CD45 on the surface of infected cells. Targeting of CD45 may prevent activation of these virus-infected T cells, possibly lengthening the life of the infected T cell so that it can harbor latent virus.

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