Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 15 of 15 for “"SHP2"”.
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Shp2 Regulates Vascular Endothelial Matrix Degradation in Phosphatase-Independent Manner
Shp2 is a protein tyrosine phosphatase that is implicated in many diseases such as developmental disorders and cancers. One of its suggested physiological functions is regulation of angiogenesis, which is often impacted in Shp2 pathologies. However, its role in angiogenesis is still poorly …
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The intramolecular domain interactions and phosphatase activation mechanisms of Shp2
Shp2 (Src Homology 2 Domain-containing Protein Tyrosine Phosphatase 2) is a pivotal player in various signaling pathways in response to growth factors. It contains two SH2 domains (N-SH2 and C-SH2), a phosphatase catalytic domain and a C-terminal tail containing two tyrosyl phosphorylation sites. …
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Signalling mechanisms of the tyrosine phosphatase SHP2 upstream of Ras
… including cancer and developmental pathologies. SHP2 regulates multiple signalling cascades, including its crucial role in the complete activation of RasMAPK in KRas driven cancers. SHP2 is also the most commonly mutated protein in RASopathies such as Noonan syndrome. SHP2 is therefore an …
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Effects of mutant SHP2 expression on heart function in Duchenne muscular dystrophy
… SH2 domain-containing tyrosine phosphatase 2 (SHP2) plays a regulatory role in several cell signaling events. Work from our lab has discovered that a loss-offunction mutation in SHP2 improves heart function after transverse aortic banding. I hypothesized that expression of a loss-of-function …
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Targeting the protein tyrosine phosphatase, SHP2, and PI3K in FLT3-ITD+ leukemia
… myeloid leukemia (AML). We hypothesized that Shp2 interacts with FLT3-ITD via protein complexes at tyrosine (Y) 768, 955, and/or 969 and that Shp2 and PI3K work cooperatively to promote FLT3-ITD-induced leukemogenesis. Consistently, mutation of N51-FLT3 tyrosine 768 to phenylalanine reduced …
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Exploring the mechanism of SHP2 and EGFR/HER2 cooperation in breast cancer cell signaling
… 2-containing protein tyrosine phosphatase 2 (SHP2) has been established as a critical mediator of cancer-related cell signaling downstream of receptor tyrosine kinases like EGFR and HER2. As such, targeting of SHP2 is being recognized as a potentially viable therapeutic option in HER2-positive …
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Funktionelle Untersuchungen zum PTPN11-Genprodukt SHP2 und zu PTPN11 Mutanten, die dem Noonan-Syndrom zugrunde liegen
… die Nichtrezeptor Protein-Tyrosin-Phosphatase SHP2, die zwei Src-homology-2 (SH2) Domänen und eine Phosphatase-Domäne besitzt. Die N-terminale SH2-Domäne (N-SH2) ist ein konformativer Schalter: entweder interagiert N-SH2 mit der Phosphatase-Domäne (PTP) und hemmt diese, oder sie bindet an ein …
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Reiterative FGF signaling determines the identity and morphology of the lacrimal gland
… FGF signaling mediated by protein phosphatase Shp2 is required for the proper patterning and differentiation of the neural crest-derived mesenchyme to produce Fgf10. Genetic evidence further demonstrates that Shp2 is recruited by Frs2α to activate Ras-MAPK signaling downstream to Fgfr1 and …
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Interrogating therapeutic resistance to oncogenic KRASG12C-based therapies in colorectal cancer
… progressing patients. We examine the role of SHP2 as a mechanism of adaptive resistance and investigate the efficacy of a KRASG12C and SHP2 inhibitor combination in our in vivo models. We show that this combination has better efficacy than the well-established KRASG12C and EGFR inhibitor …
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SALICYLALDEHYDE-TAGGED PEPTIDES FOR THE REVERSIBLE-COVALENT ENGAGEMENT OF PROTEIN LYSINE RESIDUES
… specific for two protein targets, namely SHP2 and NEMO. Moreover, using human serum albumin as model target, the CuAAC protocol was instrumental for the design of a new combinatorial approach to SA-tagged small molecules. The final part of the work, carried out at the University of Tokyo, …
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Developing a co-culture model of ovarian cancer to identify immunotherapies that can overcome TGF-β-induced immunosuppression
… effective combination treatments. SHP099, a SHP2 inhibitor that also increased GzmB expression in TGF-β-treated T cells, performed well in co-culture as a monotherapy but did not synergize with LY. However, we identified several agents that combined effectively with LY, including erlotinib, …
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Characterizing the Phosphorylation State of Tie2 using SH2 Domain Fusion Proteins
… overexpressed systems using the SH2 domains of Shp2 N-C and Grb2. As expected, phosphorylation of Tie2 in the presence of its orphan receptor Tie1 was attenuated compared to wild-type levels. Based upon available data, we anticipate this method as a useful tool to assess the phosphorylation …
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The role of adaptor proteins Crk and CrkL in lens development
… FGF signaling is controlled by the phosphatase Shp2 and the defect observed in lens fiber cell elongation can be rescued by constitutive activation of the GTPases Ras and Rac1 in the Crk and CrkL mutant lens. Interestingly, the deletion of the GTPases Rap1 in the lens showed no obvious phenotype …
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CD148: a positive regulator of GPVI and \(\alpha\)II\(\beta\)3 proximal signalling in platelets
… non-transmembrane PTPs (NTPTPs), PTP-1B, Shp1, Shp2, MEG2-PTP, LMW-PTP and HePTP and a single receptor-like PTP (RPTP), CD148, have been identified in platelets. The main objective of this thesis was to determine the functional role of CD148 in platelets, which had never been studied in …
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Identification of tumour microenvironment-derived signals that modulate the development and functionality of MDSCs
… in vitro induced intracellular signalling via SHP2, and inhibited the phagocytic capability of these cells. Moreover, persistent activation of this programme translated to an increase in their suppressive phenotype quantified by elevated expression of immune checkpoint molecules, inhibitory …