26 research outputs found
Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells
CARD 11 acts as a gatekeeper for adaptive immune responses after T cell or B cell antigen receptor (TCR/BCR) ligation on lymphocytes. PKC theta/beta-catalyzed phosphorylation of CARD11 promotes the assembly of the CARD11-BCL10-MALT1 (CBM) complex and lymphocyte activation. Here, we demonstrated that PKC theta/beta-dependent CARD11 phosphorylation also suppressed CARD11 functions in T or B cells. Through mass spectrometry-based proteomics analysis, we identified multiple constitutive and inducible CARD11 phosphorylation sites in T cells. We demonstrated that a single TCR- or BCR-inducible phosphorylation on Ser 893 in the carboxyl terminus of CARD1 1 prevented the activation of the transcription factor NF-kappa B, the kinase JNK, and the protease MALT1. Moreover, CARD11 Ser(893) phosphorylation sensitized BCR-addicted lymphoma cells to toxicity induced by Bruton's tyrosine kinase (BTK) inhibitors. Phosphorylation of Ser 893 in CARD11 by PKCO controlled the strength of CARD11 scaffolding by impairing the formation of the CBM complex. Thus, PKCO simultaneously catalyzes both stimulatory and inhibitory CARD11 phosphorylation events, which shape the strength of CARD11 signaling in lymphocytes
Einsatz der elektrolytisch-potentiostatischen Isolierung zum Studium der Reaktion des Mangans in ferritischen und austenitischen Manganstählen
The German version of De Morton Mobility Index (DEMMI) - reliability and validity for inpatient geriatric rehabilitation
The german Version of the De Morton Mobility Index (DEMMI)- Intercultural Adaptation and first clinical Results
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A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffold.
A key step in nutrient sensing is activation of the master growth regulator, mTORC1 kinase, on the lysosomal membrane. Nutrients enable mTORC1 scaffolding by a complex composed of the Rag GTPases (Rags) and Ragulator, but the underlying mechanism of mTORC1 capture is poorly understood. Combining dynamic imaging in cells and reconstituted systems, we uncover an affinity switch that controls mTORC1 lifetime and activation at the lysosome. Nutrients destabilize the Rag-Ragulator interface, causing cycling of the Rags between lysosome-bound Ragulator and the cytoplasm, and rendering mTORC1 capture contingent on simultaneous engagement of two Rag-binding interfaces. Rag GTPase domains trigger cycling by coordinately weakening binding of the C-terminal domains to Ragulator in a nucleotide-controlled manner. Cancer-specific Rag mutants override release from Ragulator and enhance mTORC1 recruitment and signalling output. Cycling in the active state sets the Rags apart from most signalling GTPases, and provides a mechanism to attenuate mTORC1 signalling
German version of the de Morton mobility index. First clinical results from the process of the cross-cultural adaptation
The English version of the de Morton Mobility Index (DEMMI) enables allied health professions in an inpatient setting to assess the mobility of geriatric patients in a reliable, valid, easy and fast way, without showing any floor or ceiling effects. The aim of this study was the DEMMI's cross-cultural adaption into German language with further analysis of some of its psychometric properties based on this process. Translation was done in a multistage procedure following international recommendations. Within clinical pilot testing the DEMMI was routinely applied over a period of 3 weeks in a geriatric hospital. User experiences were evaluated in a qualitative way and DEMMI test results were analyzed with the focus on practicability and responsiveness. A German DEMMI version has been translated and performed with 133 patients. The test takes approximately 10 min to administer, is save and easy to use and does not show any floor or ceiling effects. The DEMMI is valid for the whole mobility spectrum, that is why mobility changes can be realized sufficiently in contrast to the Timed Up And Go Test. The DEMMI is already applicable in the German-speaking world. However, further research on its validity and reproducibility are desirable
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A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffold.
A key step in nutrient sensing is activation of the master growth regulator, mTORC1 kinase, on the lysosomal membrane. Nutrients enable mTORC1 scaffolding by a complex composed of the Rag GTPases (Rags) and Ragulator, but the underlying mechanism of mTORC1 capture is poorly understood. Combining dynamic imaging in cells and reconstituted systems, we uncover an affinity switch that controls mTORC1 lifetime and activation at the lysosome. Nutrients destabilize the Rag-Ragulator interface, causing cycling of the Rags between lysosome-bound Ragulator and the cytoplasm, and rendering mTORC1 capture contingent on simultaneous engagement of two Rag-binding interfaces. Rag GTPase domains trigger cycling by coordinately weakening binding of the C-terminal domains to Ragulator in a nucleotide-controlled manner. Cancer-specific Rag mutants override release from Ragulator and enhance mTORC1 recruitment and signalling output. Cycling in the active state sets the Rags apart from most signalling GTPases, and provides a mechanism to attenuate mTORC1 signalling