Cytosolic PRKD1, 2, and 3 (protein kinase D1, D2, and D3) catalyze the phosphorylation of serine residue 132 of isoform 2 of ceramide transfer protein (CERT1-2, aka COL4A3BP-2). Protein kinase D (PRKD) is a crucial regulator of secretory transport at the trans-Golgi network (TGN). Phosphorylation of COL4A3BP-2 reduces its ceramide transfer activity. PRKDs may, therefore, act as regulators of lipid homeostasis (Fugmann et al., 2007; Kumagai et al., 2014; Shimasaki et al., 2022; reviewed by Olayioye & Hausser, 2011; Kumagai & Hanada, 2019).
β-adrenergic receptor agonists (β-agonists) mimic the action of epinephrine and norepinephrine signaling in the heart, lungs and smooth muscle tissue and have the opposite function to β-blockers. Activation of β1 receptors induces positive inotropic and chronotropic output of the cardiac muscle, leading to increased heart rate and blood pressure. Activation of β2 receptors induces smooth muscle relaxation in the lungs, GI tract, uterus and various blood vessels (Isogaya et al. 1999, Dutta & Li 2002, Ortega 2014). β-agonists are a mainstay of asthma treatment. β-agonists that bind to β1 and β2 receptors include dobutamine, arformoterol, isoprenaline and indacaterol.
Dobutamine is a sympathomimetic drug (stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system) used in the treatment of heart failure and septic or cardiogenic shock, on the basis of its positive inotropic action (Dubin et al. 2017, Rivers et al. 2001). Arformoterol is the active (R,R)-enantiomer of formoterol and is a long-lasting β2 adrenoreceptor agonist indicated for the treatment of chronic obstructive pulmonary disease (COPD) (Sears et al. 2009). Isoprenaline (isoproterenol) is the isopropylamine analog of adrenaline and is a non-selective β-adrenoreceptor agonist used in the treatment of heart block, bradycardia and as an adjunct to treat septic shock, hypoperfusion states, congestive heart failure and cardiogenic shock. Indacaterol is an ultra-long-acting β-adrenoceptor agonist used in the treatment of COPD and asthma (Beeh et al. 2007). Abediterol is an ultra-long-acting β2-agonist currently in Phase II clinical trials that is a once-daily treatment for asthma (Beier et al. 2017) and chronic obstructive pulmonary disease (COPD) (Beier et al. 2016). It shows functional selectivity for β2 receptors over β1 receptors and is a full agonist at the β2 receptor (Aparici et al. 2012).