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You searched for subject:(TULA 2). Showing records 1 – 2 of 2 total matches.

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Temple University

1. Back, Steven. TULA-2: A Novel Protein Tyrosine Phosphatase That Regulates Osteoclast Differentiation and Function.

Degree: PhD, 2014, Temple University

Cell Biology

The human skeleton is a dynamic organ that serves multiple functions to maintain normal physiology and health. It protects vital organs, provides support for movement, houses marrow and maintains calcium homeostasis. The skeleton is maintained by the work of two cells with opposing functions: osteoblasts, cells that synthesize organic bone matrix and osteoclasts that degrade and resorb it. These cells interact with one another in a tightly regulated process known as the bone remodeling cycle. This cycle maintains the health of bone by removing and replacing weak or damaged bone and responding to stress loads by remodeling portions of the skeleton that require reinforcement. Osteoblasts differentiate from mesenchymal stem cells and respond to hormonal stimuli by synthesizing and secreting cytokines necessary for osteoclast differentiation. Osteoblasts may become embedded within mineralized matrix, becoming osteocytes, cells that can sense changes in mechanical loading and facilitate localization of the remodeling cycle. Osteoclasts differentiate from hematopoietic stem cells (HSC) when the cell surface receptors, c-FMS and RANK, are activated by ligands produced by osteoblasts, M-CSF and RANKL respectively. In addition to c-FMS and RANK stimulation, another calcium-mediated, co-stimulatory pathway must be activated to ensure proper osteoclast differentiation. This pathway is activated by two immunoreceptors, OSCAR and TREM-2 that interact with adaptor proteins termed FcRγ and DAP12 respectively. These adaptor proteins harbor immunoreceptor tyrosine-based activation motifs (ITAM), which exist on their cytoplasmic tail. Once the immunoreceptors are triggered, specific tyrosines within the ITAM motifs become phosphorylated and act as docking points for the tyrosine kinase, Syk. Once bound, Syk autophosphorylates and acts on its downstream targets. Syk dephosphorylation is, therefore, necessary to attenuate this signal to prevent over activation of osteoclasts. Recently, a novel tyrosine phosphatase, T-cell Ubiquitin ligand -2 (TULA-2) has been shown to dephosphorylate specific phosphotyrosine residues on Syk in various systems and has shown an increased specificity to dephosphorylate tyrosine 352. The goal of this project is to determine how TULA-2 mediated dephosphorylation of Syk regulates osteoclast differentiation and function. TULA-2 is a member of the TULA family of proteins, TULA and TULA-2. In spite of a significant homology and similar domain organization between TULA and TULA-2, only TULA-2 has significant phosphatase activity. Furthermore, whereas TULA is expressed only in lymphocytes, TULA-2 is expressed in most tissues albeit a higher level of expression is seen in cells of hematopoietic origin. In vivo analysis including Micro-computed tomography (Micro CT) and histomorphometry indicated that mice that lack both TULA and TULA-2 (DKO) have decreased bone mass compared to wild-type (WT) counterparts. An in vitro cell differentiation assay revealed that a larger population of osteoclast-like…

Advisors/Committee Members: Sanjay, Archana, Tsygankov, Alexander;, Barbe, Mary F., Popoff, Steven N., Soprano, Dianne R., Rizzo, Victor, Hankenson, Kurt D.;.

Subjects/Keywords: Cellular biology; Biochemistry; Molecular biology;

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Back, S. (2014). TULA-2: A Novel Protein Tyrosine Phosphatase That Regulates Osteoclast Differentiation and Function. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,254886

Chicago Manual of Style (16th Edition):

Back, Steven. “TULA-2: A Novel Protein Tyrosine Phosphatase That Regulates Osteoclast Differentiation and Function.” 2014. Doctoral Dissertation, Temple University. Accessed October 23, 2020. http://digital.library.temple.edu/u?/p245801coll10,254886.

MLA Handbook (7th Edition):

Back, Steven. “TULA-2: A Novel Protein Tyrosine Phosphatase That Regulates Osteoclast Differentiation and Function.” 2014. Web. 23 Oct 2020.

Vancouver:

Back S. TULA-2: A Novel Protein Tyrosine Phosphatase That Regulates Osteoclast Differentiation and Function. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2020 Oct 23]. Available from: http://digital.library.temple.edu/u?/p245801coll10,254886.

Council of Science Editors:

Back S. TULA-2: A Novel Protein Tyrosine Phosphatase That Regulates Osteoclast Differentiation and Function. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,254886


Temple University

2. Newman, Tiffanny Nicole. ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES.

Degree: PhD, 2011, Temple University

Microbiology and Immunology

The TULA-family consists of two proteins implicated in cellular regulation. TULA-1 is expressed in T-cells and is involved in apoptosis. TULA-2 is a ubiquitously expressed phosphatase that suppresses receptor-mediated signaling. T cells from mice lacking TULA-1 and 2 (double knockout, or dKO) are hypersensitive to TCR stimulation. This may be due to these proteins having a similar function working synergistically or dissimilar functions having a convergent effect. To understand functional interaction of these proteins we have characterized TULA-family knockout mice without and during an immune challenge. We show that CD4+ T cells of dKO mice have a characteristic CD45RB distribution, and that within the CD45RBlow subset effector/memory T cells are expanded only in dKO, but not in single knockouts (sKO) of either TULA-1 or TULA-2. However, CD4+ T cells of sKO and wild-type (WT) mice respond differently to TCR stimulation as seen using signaling and responses in vitro. To evaluate consequences of TULA deficiency in vivo, we utilized two mouse models of inflammatory bowel disease: TNBS-induced colitis and colitis induced by the adoptive transfer of CD45RBhigh CD4+ T cells. Studies utilizing TNBS indicate that deficiency of any TULA-family protein exacerbates TNBS-induced colitis. Likewise, dKO CD45RBhigh CD4+ T cells were significantly more colitogenic than cells from WT mice in the transfer model. Taken together, our data indicate that TULA-family proteins are key to the physiological regulation of T-cell reactivity that drives intestinal inflammation.

Temple University – Theses

Advisors/Committee Members: Tsygankov, Alexander, Henderson, Earl E., Buttaro, Bettina A., Safadi, Fayez F., Sanjay, Archana.

Subjects/Keywords: Immunology; autoimmune; inflammatory bowel disease; phosphatase; T cells; TULA-1; TULA-2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Newman, T. N. (2011). ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,210733

Chicago Manual of Style (16th Edition):

Newman, Tiffanny Nicole. “ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES.” 2011. Doctoral Dissertation, Temple University. Accessed October 23, 2020. http://digital.library.temple.edu/u?/p245801coll10,210733.

MLA Handbook (7th Edition):

Newman, Tiffanny Nicole. “ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES.” 2011. Web. 23 Oct 2020.

Vancouver:

Newman TN. ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES. [Internet] [Doctoral dissertation]. Temple University; 2011. [cited 2020 Oct 23]. Available from: http://digital.library.temple.edu/u?/p245801coll10,210733.

Council of Science Editors:

Newman TN. ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES. [Doctoral Dissertation]. Temple University; 2011. Available from: http://digital.library.temple.edu/u?/p245801coll10,210733

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