|
|
Mebrane adaptor proteins in hematopoiesis and immune response
Pavliuchenko, Nataliia ; Brdička, Tomáš (advisor) ; Brábek, Jan (referee) ; Smrž, Daniel (referee)
Membrane adaptor proteins are proteins associated with cellular membranes that do not themselves serve as receptors. Instead, they propagate or modify the signals of these receptors by recruiting other signaling and regulatory proteins and arranging them into supramolecular complexes. In this thesis, I sought to describe selected membrane adaptor proteins and their roles in inflammation and regulation of hematopoiesis in mouse models using a reverse genetics approach. The main part of the work focused on the role of the membrane adaptor protein PSTPIP2 in suppressing inflammation. In mice, missense mutations in the Pstpip2 gene causing loss of PSTPIP2 protein lead to the development of autoinflammatory disease chronic multifocal osteomyelitis (CMO) characterized by sterile inflammatory lesions in the bones and adjacent soft tissue. These mice represent a model of the human autoinflammatory disease, chronic recurrent multifocal osteomyelitis. At the molecular level, neutrophils in the absence of PSTPIP2 exhibit pathological hyperactivity of pathways regulating IL-1β and reactive oxygen species (ROS) production, which are both implicated in the etiology of the disease. PSTPIP2 interacts with several signaling regulators, including PEST family protein tyrosine phosphatases (PEST-PTPs) and inositol...
|
guest ::
