Background and Aims: Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3) −/− mice are completely protected from ethanol-induced liver injury, Mlkl −/− mice are only partially protected. Therefore, we hypothesized that cell-specific functions of MLKL may contribute to ethanol-induced injury.Approach and Results: Bone marrow transplants between Mlkl −/− mice and littermates were conducted to distinguish the role of myeloid versus nonmyeloid

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Protein phosphorylation is a main mechanism for translating extracellular signals into cellular adaptations. In bacteria, the two-component system has been the paradigm of protein phosphorylation. Increasingly, however, protein serine/threonine and tyrosine phosphorylation (O-phosphorylation) mediated by serine/threonine protein kinases (STPKs) is identified. Mycobacterium tuberculosis (Mtb) in particular has a larger repertoire of both STPKs and O-phosphoproteins than most bacteria, suggesting a more prevalent role of STPKs in Mtb. Many studies have identified individual STPK functions and substrates, but a systems-level understanding and the full scope of Ophosphorylation in bacteria in general and Mtb in particular remains unknown. In this dissertation, we aimed to establish a systems-wide understanding of Mtb Ophosphorylation. To this end, we combined kinase loss-of-function (LoF) and gain-of-