The mobilization of metabolic energy from adipocytes depends on a tightly regulated balance between hydrolysis and resynthesis of triacylglycerides (TAGs). Hydrolysis is stimulated by b-adrenergic signalling to PKA that mediates phosphorylation of lipolytic enzymes, including hormonesensitive lipase (HSL). TAG resynthesis is associated with high-energy consumption, which when inordinate, leads to increased AMPK activity that acts to restrain hydrolysis of TAGs by inhibiting PKA-mediated activation of HSL. Here, we report that in primary mouse adipocytes, PKA associates with and phosphorylates AMPKa1 at Ser-173 to impede threonine (Thr-172) phosphorylation and thus activation of AMPKa1 by LKB1 in response to lipolytic signals. Activation of AMPKa1 by LKB1 is also blocked by PKA-mediated phosphorylation of AMPKa1 in vitro. Functional analysis of an AMPKa1 species carrying a non-phosphorylatable mutation at Ser-173 revealed a critical function of this phosphorylation for efficient release of free fatty acids and glycerol in response to PKAactivating signals. These results suggest a new mechanism of negative regulation of AMPK activity by PKA that is important for converting a lipolytic signal into an effective lipolytic response.

Acid secretion in epithelial cells is actively regulated by environmental signals, although the mechanisms by which these cues are translated into activation of H ϩ transport pathways remains the subject of intense research (11,(15)(16)(17)(18)(19). For example, the V-ATPase is regulated by several pathways, which involve CO 2 , phosphatidylinositol 3-kinase, aldolase, phosphofructokinase, actin, microtubules, and angiotensin in a variety of mammalian cellular systems (20 -27). The number of VATPases at the apical membrane of intercalated cells in the kidney increases rapidly under conditions of systemic acidosis (28, 29). Acidosis also induces H ϩ secretion via the V-ATPase through changes in intracellular [Ca 2ϩ ] concentration, calmodulin activation, the cytoskeleton, and by altering the rate of endocytosis and exocytosis in kidney cells (30).We and others have shown that regulation of the V-ATPase at the apical membrane of intercalated and clear cells is tightly linked to alkaline luminal pH, HCO 3 Ϫ , carbonic anhydrase activity, activation of the soluble adenylyl cyclase (sAC),

Lipoproteins of Gram-negative and

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