👤 Jimikaye B Courtney

Self-determination theory characterizes drinking motives according to level of autonomy and locus of control and aligns with harm reduction approaches to alcohol use. This study used latent profile analysis (LPA) to identify motivational profiles of self-determined behavioral regulations for drinking and to test their associations with sociodemographic variables and alcohol consumption and outcomes. Adults aged 18-57 (N = 630, M A four-profile model fit best. The "Aimless Drinkers" profile (n = 75, 11.9%) had low intrinsic regulation (e.g., enjoyment of drinking) and was disproportionately male (ORs = 2.35-2.65). The "Pleasure Drinker" profile (n = 114, 18.1%) had average intrinsic and low other regulations and was significantly older (OR = 1.07) than the "Externally Controlled Drinker" profile (n = 177, 28.1%), which had high external regulation (e.g., drinking due to social pressure). Externally controlled drinkers reported greater drinking intensity (M Older individuals were more likely to drink due to intrinsic enjoyment, which may reflect a shift toward greater autonomy over alcohol consumption with increasing age. Drinking primarily for enjoyment also facilitated more positive drinking outcomes. Future research should investigate whether motivational profiles of behavioral regulations for drinking predict long-term trajectories of alcohol consumption and alcohol-related risks. Show less

Protein phosphatases play an essential role in cell signaling; however, they remain understudied compared with protein kinases, in part due to a lack of appropriate tools. In order to provide conditional control over phosphatase function, we developed two different approaches for rendering MKP3 (a dual-specific phosphatase, also termed DUSP6) activatable by light. Specifically, we expressed the protein with strategically placed light-removable protecting groups in cells with an expanded genetic code. This allowed for the acute perturbation of the Ras/MAPK signaling pathway upon photoactivation in live cells. In doing so, we confirmed that MKP3 does not act as a thresholding gate for growth factor stimulation of the extracellular signal-regulated kinase (ESRK) pathway. Show less

Protein phosphatases are involved in embryonic development, metabolic homeostasis, stress response, cell cycle transitions, and many other essential biological mechanisms. Unlike kinases, protein phosphatases remain understudied and less characterized. Traditional genetic and biochemical methods have contributed significantly to our understanding; however, these methodologies lack precise and acute spatiotemporal control. Here, we report the development of a light-activated protein phosphatase, the dual specificity phosphatase 6 (DUSP6 or MKP3). Through genetic code expansion, MKP3 is placed under optical control via two different approaches: (i) incorporation of a caged cysteine into the active site for controlling catalytic activity and (ii) incorporation of a caged lysine into the kinase interaction motif for controlling the protein-protein interaction between the phosphatase and its substrate. Both strategies are expected to be applicable to the engineering of a wide range of light-activated phosphatases. Applying the optogenetically controlled MKP3 in conjunction with live cell reporters, we discover that ERK nuclear translocation is regulated in a graded manner in response to increasing MKP3 activity. Show less