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National Repository of Grey Literature 1 records found  Search took 0.01 seconds. 
Regulation of leukocyte signal transduction by adapter proteins with special focus on Csk anchoring proteins
 Drobek, Aleš ; Brdička, Tomáš (advisor) ; Brábek, Jan (referee) ; Vomastek, Tomáš (referee)
Signaling through leukocyte receptors is an integral part of immune system homeostasis and it is crucial for immune response. Signal initiation and propagation has to be properly spatiotemporally controlled not to trigger pathological immune activation. Important part in the initiation and regulation of signaling is played by adaptor proteins. These adaptors can be involved in positive or negative control, or both, depending on what effector enzymes they bind. In presented work we studied the involvement of two adaptor proteins PSTPIP2 and LST1/A in leukocyte signaling. Both adaptors interact with several inhibitory enzymes which implicates these proteins in negative regulation of signaling. We extended current understanding of why the deficiency in the expression of one of these adaptors, PSTPIP2, results in the initiation and progression of autoinflammatory disorder chronic multifocal osteomyelitis disease in mice by describing its interactions with Csk kinase and SHIP1 phosphatase. In particular we have shown that PSTPIP2 deficiency leads to increased activity of signaling pathways and increased processing of IL-1β in neutrophils in response to a variety of stimuli and that binding to SHIP1 contributes to PSTPIP2-mediated suppression of inflammation. Our biochemical analysis of the second of...
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